- Email: [email protected]
Sensitive and rapid chemiluminescence detection of propranolol based on effect of surface charge of gold nanoparticles
Journal of Luminescence 171 (2016) 238–245
Contents lists available at ScienceDirect
Journal of Luminescence journal homepage: www.elsevier.com/locate/jlumin
Full Length Article
Sensitive and rapid chemiluminescence detection of propranolol based on effect of surface charge of gold nanoparticles Yingying Qi n, Fu-Rong Xiu College of Ecological Environment and Urban Construction, Fujian University of Technology, Fuzhou 350108, PR China
art ic l e i nf o
a b s t r a c t
Article history: Received 27 June 2015 Received in revised form 30 October 2015 Accepted 14 November 2015 Available online 25 November 2015
We report a label-free, gold nanoparticles (AuNPs)-based chemiluminescent method for propranolol assay. The method relies upon the catalytic activity of unmodified AuNPs on the luminol–H2O2 chemiluminescence (CL) reaction, and the interaction of unmodified AuNPs with propranolol. The surface charge property of AuNPs directly affects their catalytic performance for CL reaction, and the interaction of AuNPs with propranolol can change AuNPs' surface charge property and induce the AuNP aggregation, and after aggregation the catalytic activity of AuNPs on the luminol–H2O2 CL reaction is greatly enhanced. During the assay, no covalent functionalization of AuNPs is required. The assay is homogenous. The detection limit of propranolol (3σ) was estimated to be as low as 6.6 10 12 g mL 1, and the sensitivity was 4 orders of magnitude better than that of known CL methods for the detection of propranolol. This AuNPs-based CL method offers the advantages of being simple, cheap, rapid, and sensitive. & 2015 Elsevier B.V. All rights reserved.
Keywords: Propranolol Chemiluminescence Gold nanoparticles Surface charge
1. Introduction Propranolol, 1-(isopropylamino)-3-(1-naphthyloxy)-2-propranolol hydrochloride (the structure is shown in Fig. 1), is a nonselective beta-adrenergic blocking drug, which is commonly used to treat several diseases such as arrhythmias, thyrotoxicosis, angina pectoris, hypertension, cardiomyopathy, myocardial infarction, essential tremor and migraine [1]. It is also misused in some sports to reduce cardiac frequency, contraction force and coronary flow [2]. The International Olympic Committee has taken propranolol as a doping substance and included it in the list of forbidden substances [3]. Owing to its therapeutical and pharmacological relevance, the rapid and accurate determination of propranolol in commercial formulations is necessary to control propranolol intake. A variety of analytic techniques, including fluorimetry [4,5], electrochemistry [6,7], electrochemiluminescence (ECL) [8] and highperformance liquid chromatography [9] have hitherto been utilized for the determination of propranolol. However, previous methods require the use of expensive instrumentation and lack sufficient sensitivity, and some of them involve long analysis times and tedious preliminary procedures such as pre-concentration in an organic solvent. Therefore, the development of high sensitivity, simple, rapid and cheap analytic method to determine propranolol in pharmaceutical preparations still has a great challenge. n
Corresponding author. Tel.: þ 86 591 22863264. E-mail address: [email protected] (Y. Qi).
http://dx.doi.org/10.1016/j.jlumin.2015.11.013 0022-2313/& 2015 Elsevier B.V. All rights reserved.
Chemiluminescence (CL) is known as a powerful and important analytical technique, because of its extremely high sensitivity along with its other advantages, such as simple instrumentation, wide calibration ranges, and suitability for miniaturization in analytical chemistry [10–15]. On the other hand, metal nanoparticles, especially precious metal nanoparticles have attracted attention in the last few years, owing to their unique structure, electronic, magnetic, optical, and catalytic properties, which have made them a very attractive material for biosensor systems and bioassays. Recently, precious metal nanoparticles also participate in the CL reaction as a catalyst, reductant, luminophor, and energy acceptor [16–19], which improve the performance of the CL system and expand its application. At the same time, precious metal nanoparticles CL assay has also been used to the determination of various drugs. Some organic medicines like isoniazid, nitrofurans and bisphenol A were determined based on silver nanoparticles (AgNPs)-catalyzed CL assay [20–22]. In order to obtain the stronger CL signal, gold nanoparticles (AuNPs) of various shapes like gold nanorod and triangular AuNPs have been used for CL analysis of organic medicament [23–25]. In addition, Au/Ag alloy nanoparticles have also been found to have catalytic ability for CL reaction, and the determination of vitamin C and anticancer drug flutamide have been developed [26,27]. Other metal nanoparticles (such as cupric oxide nanoparticles [28] and iron nanoparticles [29]) also were successively introduced to the research of CL analysis of drug. However, the preparation of these above nanoparticles required laborious procedures such as refluxing and wash, constant temperature overnight, and stabilization by the polyethylene glycol (PEG),
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
which was much more complex than that of spherical AuNPs. To the best of our knowledge, no CL analysis for the detection of propranolol involved spherical AuNPs was reported. In fact, the morphology of spherical AuNPs directly affects their catalytic performance for CL reaction. Our previous works [30–33] found that aggregated AuNPs could display stronger catalytic activity on luminol CL reaction than the dispersed AuNPs because of the decrease of the surface negative charge density of AuNPs. It was found that besides the shape and size, surface charge property of AuNPs was the important influence factor for their catalytic activity on luminol CL reaction. Additionally, AuNPs could interact with propranolol strongly and lead to AuNPs’s aggregation [34]. It is possible that during the interaction of AuNPs with propranolol, surface charge property of AuNPs would be changed. Therefore, AuNPs's aggregation induced by propranolol offers the possibility of applying this phenomenon to direct AuNPs–CL assay propranolol. The applicability of aggregated AuNPs used in the direct AuNPs–CL assay propranolol depends on whether or not the aggregated AuNPs induced by propranolol show different catalytic activity for the CL reaction. In this work, the catalytic ability of aggregated AuNPs induced by propranolol on the luminol CL system was first studied. It was found that aggregated AuNPs induced by propranolol could also enhance the luminol CL signal in comparison with dispersed AuNPs. Based on this finding, the luminol–H2O2–aggregated AuNPs CL system was utilized to develop a new and simple AuNPs–CL protocol for the determination of propranolol. A schematic diagram of this method is shown in Scheme 1. In the absence of propranolol, AuNPs had high negative charge density and was monodispersed, and could induce a weak CL signal of luminol–H2O2 system. In the presence of propranolol, the interaction of propranolol and AuNPs could reduce surface negative charge density of AuNPs and cause AuNPs's aggregation, and initiate a strong CL signal.
2. Experimental 2.1. Chemical and reagents Propranolol was purchased from National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China).
O
N H OH
. HCl Fig. 1. Structure of propranolol hydrochloride.
239
The tablets containing propranolol was purchased from Lijun Pharmaceutical Co., Ltd. (Xi'an, China). Chloroauric acid (HAuCl4 4H2O) was purchased from Sinopharm Chemical Reagent Company (Shanghai, China). Sodium citrate and sodium hydroborate (NaBH4) were purchased from Tianjing Chemical Reagent Company (Tianjing, China). Other reagents and chemicals were of analytical grade and used without further purification. Doubly distilled and deionized water was used throughout. Luminol stock solution (2.5 10 2 M) was prepared by dissolving 4.43 g luminol in 20 mL of 0.10 M NaOH and then diluting to 1 L with water. The luminol solution was stored in dark for one week prior to use ensured that the reagent property had stabilized. Working solutions of luminol were prepared by diluting the stock solution. Working solutions of H2O2 were prepared fresh daily from 30% (w/w) H2O2. 2.2. Apparatus The CL intensity was measured and recorded on an IFFL-D chemiluminescence analyzer (Xi'an Ruimai Electronic Sci. Tech. Co. Ltd., Xi'an, China). UV–visible adsorption spectra were recorded on a Hitachi U-3900H UV–vis spectrophotometer. The transmission electron microscopy (TEM) images of AuNPs were taken by using a JEM-2100 TEM (Japan Electronics Co., Ltd.). The determination of zeta potential was carried out by Malvern Zetasizer 2000. The pH detections were carried out on a PHS-3E analyzer (Jiangsu, China). 2.3. Synthesis of AuNPs All glassware used in these preparations was thoroughly cleaned in aqua regia (1:3 HNO3–HCl), rinsed in doubly distilled water, and oven-dried prior to use. 2.6 nm AuNPs were prepared by hydroborate reduction method [35]. Briefly, 100 mL of 0.01% HAuCl4 solution under vigorous stirring was mixed with 1 mL of 1% trisodium citrate and 1 mL of 0.075% NaBH4/1% trisodium citrate solution at room temperature. The mixed solution was stirred for 30 min and then stored in 4 °C refrigerator before use. 6 nm AuNPs were also synthesized by hydroborate reduction method [35]. In brief, 0.40 mL of 1% trisodium citrate solution was added into 100 mL of 0.01% HAuCl4 solution and stirred for 1 min. Then 0.15 mL of 0.075% NaBH4/1% trisodium citrate solution was added and stirred for another 15 min and then stored in 4 °C refrigerator before use. AuNPs with the diameters of 16 nm and 25 nm were synthesized by sodium citrate reduction method [36,37]. For the synthesis of 16 nm AuNPs, 100 mL of 0.01% HAuCl4 solution was heated to boil. 2 mL of 1% trisodium citrate solution was rapidly added into HAuCl4 solution with vigorously stirring and remained at boiling for 15 min. The heating source was then removed and the solution was continuously stirred for another 15 min. The procedures for the synthesis of 25 nm AuNPs were similar to that of 16 nm AuNPs by decreasing the added volume of 1% trisodium
Scheme 1. Schematic representation of the proposed CL assay for propranolol.
240
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
citrate from 2.0 mL to 1.5 mL. The as-prepared AuNPs solutions were stored in a 4 °C refrigerator. 2.4. Procedure for the CL detection of propranolol The whole procedure could be divided into two stages: (1) the interaction between propranolol and AuNPs, and (2) CL detection. A standard CL detection of propranolol was realized as following procedure: first, 200 mL AuNPs solution was mixed with 200 mL propranolol solutions with different concentrations, the mixed solution was incubated for 3 min at the room temperature, leading to the aggregation of AuNPs. Second, after the interaction between propranolol and AuNPs, a 100 μL above AuNPs/propranolol solution was pipetted into a 40 14 mm2 quartz tube (used as CL reactor), then 200 μL luminol–H2O2 CL solution (the volume ratio of 5 10 4 M luminol and 5.0 10 2 M H2O2 was 2:1) was injected, and the CL signal was measured and recorded with the IFFL-D Chemiluminescence Analyzer. The concentration of propranolol was quantified by the CL intensity. The CL experiments in this work were not consecutive measurements.
3. Results and discussion 3.1. Change of 6 nm AuNPs induced by propranolol The prepared AuNPs (E6 nm) in aqueous solution are stable, as a result of the electrostatic repulsion of the negative capping agent (e.g. citrate ion) against the van der Waals attraction between AuNPs [38]. The AuNPs have a surface plasma resonance (SPR) absorption peak at about λ ¼520 nm and appear pink [39]. Propranolol could interact readily with AuNPs and induce the aggregation of AuNPs [34]. The aggregated AuNPs have a broad SPR absorption in the range of λ ¼ 550–850 nm. UV/vis spectroscopy was used to explore the change of AuNPs state induced by propranolol in this system. As shown in Fig. 2A, the AuNPs in the absence of propranolol have a SPR absorption peak at λ ¼520 nm; after the action of propranolol, the absorption spectrum for the AuNPs is broad and featureless, which indicates that the aggregation of AuNPs appears. The results were consistent with the transmission electron microscopy (TEM) images (Fig. 2B). The mechanism behind the phenomenon lies in the interaction between propranolol and AuNPs. It is known that SPR is the coherent excitation of all the ‘‘free’’ electrons within the conduction band, leading to an inphase oscillation. In fact, SPR of AuNPs mainly depends on the dipole moment of particles; that is to say, it is closely related to its surface states and the substance adsorbed on the surface of particles [40,41]. In addition, it was reported that citrate ions on the surface of AuNPs could be readily replaced by – NH– ligand in organic compounds [42]. So, in the presence of propranolol, citrate ions on the surface of AuNPs are replaced by the –NH– group in the structure of propranolol. The replacement of citrate ions with propranolol reduced the negative charge density on the surfaces of AuNPs and resulted in the loss of negative charge repulsion of AuNPs [41]. Consequently, the propranolol induced the aggregation of AuNPs. 3.2. Enhancement of the catalytic activity of AuNPs after the action of propranolol The luminol–H2O2 system can be effectively catalyzed by some metal nanoparticles. Cui and co-workers first discovered the catalytic activity of AuNPs in the luminol–H2O2 system, and found that the size of AuNPs was an important influence factor for their catalytic activity [16]. In our previous study, the electron density in the conduction bands of AuNPs and the surface-charge density of
Fig. 2. (A) UV–visible absorption spectra of AuNPs in the absence and presence of propranolol and (B) TEM images of 6 nm. AuNPs (a), and AuNPs after the adding of propranolol (b).
AuNPs were found to also have a significant influence on the catalytic activity of AuNPs in luminol–H2O2–AuNPs CL system [31– 33]. Hence, the catalytic activity of AuNPs must be relevant to the substance adsorbed on their surface, because the adsorbed substance can directly alter the size, morphology, and surface state of AuNPs, and further affect their microcosmic property such as conduction bands electron density and surface charge density. In the interaction between propranolol and AuNP, citrate ions on the surface of AuNPs were replaced by the –NH– group in the structure of propranolol so that AuNPs losed strong electrostatic repulsion of the electronegative capping agent citrate ion, and the morphology of AuNPs was transformed from dispersed state to aggregated state. We investigated the effect of propranolol on the catalytic activity of AuNPs in the luminol–H2O2 system. The CL behavior of the luminol–H2O2–AuNPs system was determined as the surface of AuNPs (E6 nm) was surrounded by propranolol. As shown in Fig. 3, propranolol itself could slightly inhibit the CL signal of luminol–H2O2 reaction in the absence of AuNPs, probably because that propranolol competed with luminol for H2O2 and the amount of the oxidant reacting with luminol was reduced. It also can be found from Fig. 3 that the AuNPs showed a certain degree of catalytic activity for the luminol–H2O2 system before adding propranolol. However, it is interesting to find that the aggregated AuNPs showed a rather strong catalytic activity, more than the dispersed AuNPs, after the introduction of propranolol in luminol–H2O2 system. Based on our previous study [30–33], the catalytic activity of AuNPs for luminol–H2O2 system may be influenced by the electron density in the conduction bands of AuNPs and the surface-charge density of AuNPs, indicating that more than one parameter was playing its sole to influence the catalytic activity of AuNPs. It is considered that higher electron density in the conduction bands would be favorable for the particle-mediated electron transfer processes and lead to higher catalytic activity [33]. The strong electric charge accumulation and oscillation effects occured in nanoparticles' specific sites would lead to the enhancement of SPR absorption, and SPR absorption
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
241
According to the above proposed mechanism for AuNPs catalytic activity enhancement, we further speculated that the cationic AuNPs with higher zeta potential value would show a higher catalytic activity than the anionic AuNPs, because the anionic HO2 (or anionic luminol) can easily interact with cationic AuNPs. To validate the scenario, we prepared amine modified cationic AuNPs (the preparation procedure is presented in Supporting information) and detected its zeta potential [43]. Zeta potential of the cationic AuNPs was þ32.6 mV. Indeed, this cationic AuNPs showed superstrong catalytic property, which was far more than the anionic AuNPs (Fig. 3). Therefore, we reasoned that propranolol could result in a remarkable increase of catalytic activity of AuNPs on the luminol–H2O2 CL system mainly because of the change of the surface charge property of AuNPs. Fig. 3. Effects of 6 nm AuNPs and cationic AuNPs on the luminol–H2O2 CL reaction. Conditions: luminol, 5 10 4 M; H2O2, 5.0 10 2 M.
intensity from UV–vis absorption spectra is considered to be able to indicate the electron density in the conduction bands of nanoparticles [40]. However, UV–vis absorption spectra of aggregated AuNPs in the presence of propranolol did not rise but decreased slightly when compared with the dispersed AuNPs (Fig. 2A), indicating that the electron density in the conduction bands of aggregated AuNPs induced by propranolol was not higher than that of dispersed AuNPs. Therefore, in the luminol–H2O2–AuNPs– propranolol CL catalytic system, the electron density in the conduction bands of AuNPs was not supposed to be the main influence factor, there must be other ones that played their roles. We reasoned that the enhancement effect of the aggregated AuNPs induced by propranolol may be attributed to the change of the AuNPs surface-charge density. Analysis results revealed that the zeta potentials of the dispersed AuNPs (E6 nm) and the aggregated AuNPs (E 6 nm) were 40.8 and þ0.28 mV, respectively. It is clear that the surface negative charge density of AuNP is greatly decreased, and charge property is actually changed from negative charge to positive charge after the aggregation of AuNP induced by propranolol. For the luminol–H2O2 CL system, the optimized pH conditions are generally about 11–12. The hydroperoxide ion (HO2 ), easily formed in strong alkaline medium, has an acid–base equilibrium (pKa ¼ 11.7) with H2O2. Similarly, the luminol anion is the main molecular form of luminol in strong alkaline medium. The anionic HO2 (or anionic luminol) does not easily interact with the anionic AuNPs whose surface is surrounded by citrate ions due to the electrostatic repulsion. The dispersed AuNPs, which have a high surface negative charge density ( 40.8 mV), have a rather low catalytic effect on the luminol–H2O2 CL reaction. The replacement of citrate ions on the surface of AuNPs by the –NH– group in the structure of propranolol loses its ability to protect the AuNPs. The –NH– group can screen the repulsion between the negatively charged AuNPs, and the zeta potential of AuNPs after propranolol's action was changed to be þ0.28 mV, which lead to the aggregation of the AuNPs. This is consistent with the previous reports in which AuNPs aggregated when its zeta potential Z 30 mV and r þ 30 mV [41]. The aggregated AuNPs with zeta potential þ0.28 mV can more easily interact with the anionic HO2 (or anionic luminol), resulting in a higher catalytic effect on the luminol–H2O2 reaction (Fig. 3). It is clear that the conversion of aggregation state before and after AuNPs–propranolol interaction would be easily distinguishable by a CL analysis of the luminol– H2O2 CL system. Hence, we reasoned that the change of the surface charge density of AuNPs resulted in the enhanced catalysis of the aggregated AuNPs.
3.3. Optimization of assay conditions Based on the principle of the AuNPs CL sensing for propranolol, there are two main actions: the AuNPs–propranolol interaction and AuNPs' catalysis for the luminol–H2O2 CL reaction. Two strategies were developed for the analysis: Strategy 1: the AuNPs and the propranolol solution were first mixed and allowed to incubate for a set period, and then the luminol/H2O2 mixed solution was injected into the AuNPs solution. Strategy 2: the AuNPs, propranolol and luminol solution were first mixed in reactor, and then the H2O2 solution was injected into the mixed solution. Analysis of the experimental results revealed that the sensitivity of AuNPs CL method in Strategy 1 was higher than that of Strategy 2. In this AuNPs CL method for propranolol, the AuNPs–propranolol interaction is the replacement process of substance adsorbed on the surface of particles and is the key factor for the detection of propranolol. In Strategy 1, the replacement is completely separate from detection so that it can be done under optimal conditions. In Strategy 2, luminol might influence the ion replacement process. This may be the reason why the sensitivity in Strategy 2 is lower. Moreover, it is well known that the luminol–H2O2 CL reaction is very slow and weak CL reaction in the absence of a catalyst. Thus, we chose Strategy 1 (shown in Scheme 1) as the analytical strategy for the assay. With a fixed strategy, the performance of the developed CL method is still strongly influenced by the assay conditions, such as, AuNPs size and concentration, and the CL reaction conditions. Different assay conditions were investigated in our studies. The size and concentration of AuNPs, the vital parameters for propranolol detection, were explored. In this system, AuNPs are the signal element and the size of the AuNPs influences the propranolol–AuNP interaction. Simultaneously, the size of the AuNPs also affects the catalytic activity of AuNPs in the luminol–H2O2 CL reaction. The previous studies showed that in the small size range, the increasing size of the AuNPs resulted in an increase in catalytic activity [16]. For this CL method, the CL signal from the dispersed AuNPs is taken as the background. Therefore, the small-sized AuNPs should be used to achieve high sensitivity. As shown in Fig. 4A, all of the examined AuNPs had the enhancement on the CL reaction. The CL intensity increased with increasing particle size from 2.6 to 6 nm AuNPs. This might be attributed to Fermi level shift, which leads to an alteration of the energy gap for particlemediated electron-transfer processes [44]. For larger particles (from 6 to 25 nm diameter), the CL intensity decreased with increasing particle size, probably because that the particles of smaller size have higher numbers of active sites on their surfaces for a given amount of catalyst material, which lead to a higher rate of catalytic reaction [44]. Therefore, we used the 6 nm AuNPs in this CL method. The sensitivity of the CL method is also influenced by the AuNPs concentration. If the AuNPs concentration is too high, the system is not sensitive enough to detect small amounts
242
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
Fig. 4. Effects of reactant conditions on the CL intensity. (A) The size and concentration of AuNPs; reaction conditions: 5 10 4 M luminol, 5.0 10 2 M H2O2, pH 12.0. (B) Luminol concentration; reaction conditions: pH 12.0, 5.0 10 2 M H2O2, 1.6 10 4 M AuNPs (6 nm). (C) H2O2 concentration; reaction conditions: pH 12.0, 5 10 4 M luminol, 1.6 10 4 M AuNPs (6 nm). (D) pH ; reaction conditions: 5 10 4 M luminol, 5.0 10 2 M H2O2, (6 nm) 1.6 10 4 M AuNPs (6 nm). The concentration of propranolol in all reaction conditions was 1 10 8 g mL 1.
of propranolol and does not differentiate them from the background. From Fig. 4A, the CL intensity increased with increase of the concentration of 6 nm AuNPs solution up to 1.6 10 4 M. Above this concentration, the CL intensity decreased. The reason might be that AuNPs in high concentration undergone strong interactions among these particles and the CL energy transfer occurred [21]. So, in this system, we used 1.6 10 4 M of AuNPs (E 6 nm) for all experiments. Furthermore, we investigated the effect of the age of the AuNPs. For the same concentration of propranolol, the signal did not change for the fresh AuNPs over one week, but the sensitivity decreased markedly if the AuNPs were stored for a month or more. The reason is that the AuNPs themselves aggregate during the stored time. For this reason we prepared very dilute AuNPs solutions on a weekly basis for our experiments. The important experimental parameters influencing the CL reaction of luminol–H2O2–6 nm AuNPs, including the concentrations of luminol and H2O2, and media pH, were optimized. Fig. 4B showed the effect of luminol concentration on the CL reaction. It was found that in the range of 0.01–0.5 mM the CL intensity increased with increasing luminol concentration. When the luminol concentration was higher than 0.5 mM, the CL intensity decreased. The possible reason is that luminol of high concentration could produce self-absorption of the emitted radiation and decrease the CL intensity [28]. In addition, it was also reported that the increase of ionic strength could cause the CL decrease [45]. Because the luminol solution was prepared by dissolving luminol in NaOH solution, ionic strength of the system increased with the
increase of luminol concentration, leading to the decrease of CL intensity. The effect of the H2O2 concentration on the CL was studied in the range of 0.01–200 mM (Fig. 4C), and the CL signal rose fast at first between 0.001 and 5 10 2 M, then very slowly, and remained almost constant above 5 10 2 M. The experimental results showed that the optimal pH for this CL system was 12.0 (Fig. 4D), which is in agreement with the results of previous studies [30,32]. 3.4. Analytical performance of this CL assay for propranolol Under the optimized conditions, experiments were carried out by adding increasing amounts of propranolol to the CL method to examine whether the CL change could be used for propranolol quantification. As shown in Fig. 5, the CL intensity increases with the increasing propranolol concentration. The CL intensity of this CL system was linear with the concentration of propranolol in the range from 8.2 10 11 to 8.6 10 8 g mL 1 (Fig. 6). The relative standard deviation (RSD) was 3.8% for 6.6 10 9 g mL 1 propranolol, calculated after studying six replicate injections of luminol– H2O2 CL reagents. The detection limit is an estimate of the concentration at which we can be fairly certain that the compound is present, concentrations below which may not be detected; for this experiment it was estimated to be 6.6 10 12 g mL 1 using 3σ. Compared with the previously reported results in Table 1, the increase in sensitivity of this system is 4 orders of magnitude more than that of the known CL method for the detection of propranolol [6], and the detection limit attained that reported for an ECL
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
sensor for propranolol [11]. The sensitivity of the proposed method is, therefore, feasible. In order to assess the possible application of the proposed method, the influence of commonly used excipients and additives in pharmaceutical formulations and potential interference in human urine samples was investigated for the determination of 8.2 10 11 g mL 1 propranolol. The tolerable limit of a foreign species was taken as a relative error of less than 5%. No interference could be found when the sample included up to 2000-fold K þ , NO3 ; SO24 ; CLO4 , Cl , Br , F , and 1000-fold NH4þ , glucose, maltose, ascorbic acid, citric acid, starch, sorbitol and sucrose, and 500-fold Mg2 þ , Al3 þ , CO23 , threonine, tryptophane, cyclodextrin and fructose, 100-fold Fe3 þ , Fe2 þ , Ca2 þ , Mn3 þ , methionine, alanine, thiourea, gelatine, urea and lactose. The selectivity of the proposed method was therefore evident. In the proposed method, the response of propranolol to CL signal was based on that in the interaction of propranolol and AuNPs, the replacement of citrate ions on AuNPs surface by the –NH– group in propranolol structure led to the change of AuNPs surface charge property, and AuNPs showed aggregation and an enhancement of catalytic activity. Actually, the difference in the change extent of AuNPs surface charge property could result in different aggregation and different enhancement of catalytic activity, which agreed with our previous research [32]. He et al. [46] developed Rayleigh light scattering (RLS) method for propranolol detection by AuNPs' aggregation induced by propranolol and the increasement of RLS intensity. In He's method, the interactions between AuNPs and many other doping agents (such as caffeine, furosemide, spironolactone, hydrochlorothiazide, methyltestosterone, testosterone, benzthiazide
Fig. 5. CL signals for triplicate measurement of AuNPs in different concentration propranolol. The concentrations of propranolol: (a) 0gmL 1, (b) 8.2 10 11gmL 1, (c) 2.6 10 10gmL 1, (d) 5.6 10 10gmL 1, (e) 8.9 10 10gmL 1, (f) 1.2 10 9gmL 1, (g) 6.6 10 9gmL 1, (h) 3.6 10 8g mL 1, (i) 6.2 10 8gmL 1, and (j) 8.6 10 8gmL 1. Conditions: luminol, 5 10 4M; H2O2, 5.0 10 2M.
243
and acetazolamide) could not lead to color change and AuNPs aggregation. In addition, they also found that other foreign substances such as metal ions, negative ions and amino acid also could not disturb the action between AuNPs and propranolol [46]. Hence, the possible reason for the good selectivity of the proposed method is that the interaction between foreign species and AuNPs is very weak, and the change extent of AuNPs surface charge property is very ‘micro’, so the catalytic activity enhancement is extremely weak when compared to propranolol. This result is similar to the good selectivity of He's Rayleigh light scattering (RLS) method for propranolol detection based on AuNPs aggregation [46]. 3.5. Determination of propranolol in tablets Commercial pharmaceutical propranolol samples (tablets) were analyzed to determine the substance in order to evaluate the validity of the proposed method. A tablet sample equivalent to approximately 10 mg of propranolol was weighed accurately and ground to a fine powder, and mixed homogeneously, and then dissolved in 10.0 mL of water. The resultant solution was filtered to remove any insoluble substances. The results are listed in Table 2. It can be seen that there was no significant difference between the results obtained by the proposed method and the Chinese pharmacopoeia method, by measurement of absorbance at 290 nm [47]. The feasibility of the CL method for the determination of propranolol is, therefore, evident. The method may be suitable for propranolol determination in medicine. 3.6. Determination of propranolol in spiked human urine To further test the possibility of applying this method to real biological samples, human urine samples added different concentrations of propranolol were analyzed. The urine samples were collected from different healthy volunteers. According to the references [48], known amount of propranolol standard solution was added into 1.0 mL of urine sample. The solution was gently vortex-mixed with 1.00 mL of 2% ZnSO4 solution and 1.00 mL of 1.8% Ba(OH)2 solution to remove possible reducing substances, and then centrifuged at 5000 r/min for 20 min. The supernatant was diluted to appropriate concentration. Blank experiment was also carried out with the same procedure without adding propranolol. The results are shown in Table 3. It could be seen that the recovery and precision of this method were satisfactory. Moreover, the sample in our method was pretreated by ZnSO4–Ba(OH)2 solution removing possible reducing substances and centrifugation to obtain supernatant, and process time is within a mere half-hour. Sample pretreatment in other methods need hydrochloric acid
Fig. 6. Calibration curve of CL intensity versus propranolol concentration. The concentrations of propranolol: (A) 8.2 10 11–1.2 10 9 g mL 1, (B) 1.2 10 9– 8.6 10 8 g mL 1.
244
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
Table 1 A comparison of various methods for the determination of propranolol. Analytical technique
Reagents used and comments
Analytical ranges (g mL 1)
Detection limit (g mL 1)
Reference
Fluorescence Fluorescence ECL
Amberlite XAD-7 as solid support at 20 °C Sodium dodecyl sulfate, using feed-forward neural networks
0–1 10 7 1.06 10 9–5.32 10 7 2.96 10 11–1.48 10 9
2 10 10 2.3 10 10 8.87 10 12
[5] [4] [8]
1.75 10 7–1 10 6 2.01 10 5–1.51 10 4 0–2.0 10 5 8.2 10 11–8.6 10 8 5.9 10 8–2.66 10 6 1.48 10 7–1.48 10 5 2.01 10 10–1.36 10 7
7 10 8 ─ 3.8 10 8 6.6 10 12 5.3 10 8 1.48 10 9 5.03 10 11
[12] [11] [10] This method [6] [7] [9]
CL CL CL CL Voltammetry Electrochemistry Chromatography
2þ RuðbpyÞ3 ,
graphene as modified material Acid potassium permanganate reaction The oxidation of propranolol by acidic potassium permanganate Pyrogallol oxidized by periodate AuNPs-catalyzed luminol reaction Cathodically pretreated borondoped diamond electrode Britton–Robinson solutions, pulse polarography pH 2.0–12.0 Solid phase extraction and detected by tandem mass spectrometry with a turbo ionspray interface
Acknowledgments
Table 2 Determination of propranolol in tablets (mg/tablet). Samples
Claimed content
Present method
RSD (n¼ 5)%
Pharmacopoeia method
RSD (n¼ 5)%
1 2 3
10 10 10
9.82 9.65 10.38
1.6 0.6 2.5
9.76 10.18 10.29
2.1 1.5 0.9
This work was supported financially by Program for New Century Excellent Talents in Fujian Province University, the Natural Science Foundation of Fujian Province of China (2014J01167 and 2015J01034) and the Scientific Research Foundation of Fujian University of Technology (GY-Z10054 and GY-Z10055).
Appendix A. Supplementary material
Table 3 Determination of propranolol in spiked human urine. Samples
Added (10 3 mg L 1)
Found (10 3 mg L 1)
RSD (n¼ 5)%
Recovery %
No. 1 No. 2 No. 3 No. 4 No. 5
0.00 2.00 4.00 6.00 8.00
0.00 1.98 4.18 5.75 7.68
– 1.6 2.8 2.5 3.2
– 99.0 104.5 95.8 96.0
processing for over 24 h, and vacuum evaporation to dryness at room temperature using a rotary evaporator, and then dissolving residue to get the sample solution. So, sample pretreatment of our methods is more easy and convenient than that of other methods.
4. Conclusions In summary, a novel and sensitive strategy to convert the AuNPs–propranolol interaction event into CL signals by employing unmodified AuNPs as signaling probes is proposed in this study. This strategy has several significant advantages: 1) the AuNPs does not need labeling or modifying, so that the affinity of the original AuNPs is not changed by a label, and the method is simple, cheap, and easy to operate. 2) The assay is homogenous and occurs in the liquid phase, which makes it easy to automate by standard robotic manipulation of microwell plates. 3) The assay avoids the separation and washing steps, and the whole detection can be completed in 30 min. 4) The AuNPs–propranolol interaction is separated from the detection so that the interaction and the detection could occur in their own optimal condition, respectively. So, it offers high sensitivity. In addition, given the simplicity and sensitivity of CL detection, this study holds great promise for the analysis of pharmaceutical compounds, and may pave a general way to the development of AuNPs-based CL methods for a broad range of analytes.
Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.jlumin.2015.11.013.
References [1] T.P. Ruiz, C.M. Lozano, V. Tomás, J. Carpena, Talanta 45 (1998) 969. [2] J.A. Murillo-Pulgarıń, A. Alanõń-Molina, P. FernańdezLopʹ ez, Anal. Chim. Acta 370 (1998) 9. [3] P. Valderrama, R.J. Poppi, Anal. Chim. Acta 651 (2009) 31. [4] T. Madrakian, A. Afkhami, M. Mohammadnejad, Talanta 78 (2009) 1051. [5] J.F. Fernańdez-Sańchez, A.S. Carretero, C. Cruces-Blanco, A. Fernańdez-Gutieŕrez, J. Pharm. Biomed. Anal. 31 (2003) 859. [6] E.R. Sartori, R.A. Medeiros, R.C. Rocha-Filho, O.F. Fatibello, Talanta 81 (2010) 1418. [7] M.A. El-Ries, M.M. Abou-Sekkina, A.A. Wassel, J. Pharm. Biomed. Anal. 30 (2002) 837. [8] H. Qi, C. Wang, R. Zou, L. Li, Anal. Methods 3 (2011) 446. [9] P. Partani, Y. Modhave, S. Gurule, A. Khuroo, T. Monif, J. Pharm. Biomed. Anal. 50 (2009) 966. [10] G.Z. Tsogas, D.V. Stergiou, A.G. Vlessidis, N.P. Evmiridis, Anal. Chim. Acta 541 (2005) 149. [11] K.L. Marques, J.L.M. Santos, J.L.F.C. Lima, J. Pharm. Biomed. Anal. 39 (2005) 886. ́ M.T.A. Pardo, Anal. Chim. Acta 488 (2003) 81. [12] A. Townshend, J.A.M. Pulgarın, [13] S. Zhao, X. Li, Y.M. Liu, Anal. Chem. 81 (2009) 3873. [14] Z. Wang, S.Y. Chin, C.D. Chin, J. Sarik, M. Harper, J. Justman, S.K. Sia, Anal. Chem. 82 (2010) 36. [15] C. Dodeigne, L. Thunus, R. Lejeune, Talanta 51 (2000) 415. [16] Z.F. Zhang, H. Cui, C.Z. Lai, L.J. Liu, Anal. Chem. 77 (2005) 3324. [17] C.F. Duan, H. Cui, Chem. Commun. 18 (2009) 2574. [18] S. Gupta, S. Huda, P.K. Kilpatrick, O.D. Velev, Anal. Chem. 79 (2007) 3810. [19] J.M. Lin, M.L. Liu, J. Phys. Chem. B 112 (2008) 7850. [20] B. Haghighi, S. Bozorgzadeh, Microchem. J. 95 (2010) 192. [21] X. Chen, C. Wang, X. Tan, J. Wang, Anal. Chim. Acta 689 (2011) 92. [22] W. Liu, J. Kou, X. Jiang, Z. Zhang, H. Qi, J. Lumin. 132 (2012) 1048. [23] J.X. Du, J. Quan, Y.D. Wang, Talanta 90 (2012) 117. [24] C. Lu, Q.Q. Li, S. Chen, L.X. Zhao, Z.X. Zheng, Talanta 85 (2011) 476. [25] Q.S. Chen, S.L. Bai, C. Lu, Talanta 89 (2012) 142. [26] M.J. Chaichi, S.N. Azizi, M. Heidarpour, Spectrochim. Acta Part A 116 (2013) 594. [27] M.J. Chaichin, S.O. Alijanpour, J. Lumin. 134 (2013) 195. [28] W. Chen, L. Hong, A.L. Liu, J.Q. Liu, X.H. Lin, X.H. Xia, Talanta 99 (2012) 643. [29] B. Rezaei, A.A. Ensafi, L. Zarei, Spectrochim. Acta Part A 90 (2012) 223. [30] Y. Qi, B. Li, Chem. Eur. J. 17 (2011) 1642. [31] Y. Qi, B. Li, Spectrochim. Acta Part A 111 (2013) 1. [32] Y. Qi, B. Li, Z. Zhang, Biosens. Bioelectron. 24 (2009) 3581. [33] Y. Qi, F.R. Xiu, B. Li, Anal. Biochem. 449 (2014) 1. [34] R. Stiufiuc, C. Iacovita, G. Stiufiuc, E. Bodoki, V. Chis, C.M. Lucaciu, Phys. Chem. Chem. Phys. 17 (2015) 1281.
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
[35] [36] [37] [38] [39] [40] [41] [42]
K.R. Brown, A.P. Fox, M.J. Natan, J. Am. Chem. Soc. 118 (1996) 1154. G. Frens, Nat. Phys. Sci. 241 (1973) 20. Z.F. Zhang, H. Cui, M.J. Shi, Phys. Chem. Chem. Phys. 8 (2006) 1017. K.C. Grabar, R.G. Freeman, M.B. Hommer, M.J. Natan, Anal. Chem. 67 (1995) 735. H. Li, L.J. Rothberg, J. Am. Chem. Soc. 126 (2004) 10958. S. Link, M.A. El-sayed, Int. Rev. Phys. Chem. 19 (2000) 409. C. Kyungnam, L. Yunhee, L.H. Chang, L. Kangtaek, K. Youngmin, C. Hyoungwoo, R.D. Pan, L.Y. So, J.W. Sang, J. Phys. Chem. C 112 (2008) 8629. V. Selvaraj, M. Alagar, Int. J. Pharm. 337 (2007) 275.
245
[43] T. Niidome, K. Nakashima, H. Takahashi, Y. Niidome, Chem. Commun. 17 (2004) 1978. [44] R.K. Sharma, P. Sharma, A. Maitra, J. Colloid Interface Sci. 265 (2003) 134. [45] M. Yang, R. Liu, Y. Xu, Y. Zou, X. Song, Biosens. Bioelectron. 22 (2007) 871. [46] H.Y. Duan, F. Chen, X.P. Ai, Z.K. He, Chin. Chem. Lett. 16 (2005) 947. [47] Chinese Pharmacopoeia Commission, The Pharmacopoeia of People's Republic of China (Part II), Chemical Industry Press, Beijing (2000), p. 683. [48] D.C. Williams, G.F. Huff, W.R. Seltz, Clin. Chem. 22 (1976) 372.
Contents lists available at ScienceDirect
Journal of Luminescence journal homepage: www.elsevier.com/locate/jlumin
Full Length Article
Sensitive and rapid chemiluminescence detection of propranolol based on effect of surface charge of gold nanoparticles Yingying Qi n, Fu-Rong Xiu College of Ecological Environment and Urban Construction, Fujian University of Technology, Fuzhou 350108, PR China
art ic l e i nf o
a b s t r a c t
Article history: Received 27 June 2015 Received in revised form 30 October 2015 Accepted 14 November 2015 Available online 25 November 2015
We report a label-free, gold nanoparticles (AuNPs)-based chemiluminescent method for propranolol assay. The method relies upon the catalytic activity of unmodified AuNPs on the luminol–H2O2 chemiluminescence (CL) reaction, and the interaction of unmodified AuNPs with propranolol. The surface charge property of AuNPs directly affects their catalytic performance for CL reaction, and the interaction of AuNPs with propranolol can change AuNPs' surface charge property and induce the AuNP aggregation, and after aggregation the catalytic activity of AuNPs on the luminol–H2O2 CL reaction is greatly enhanced. During the assay, no covalent functionalization of AuNPs is required. The assay is homogenous. The detection limit of propranolol (3σ) was estimated to be as low as 6.6 10 12 g mL 1, and the sensitivity was 4 orders of magnitude better than that of known CL methods for the detection of propranolol. This AuNPs-based CL method offers the advantages of being simple, cheap, rapid, and sensitive. & 2015 Elsevier B.V. All rights reserved.
Keywords: Propranolol Chemiluminescence Gold nanoparticles Surface charge
1. Introduction Propranolol, 1-(isopropylamino)-3-(1-naphthyloxy)-2-propranolol hydrochloride (the structure is shown in Fig. 1), is a nonselective beta-adrenergic blocking drug, which is commonly used to treat several diseases such as arrhythmias, thyrotoxicosis, angina pectoris, hypertension, cardiomyopathy, myocardial infarction, essential tremor and migraine [1]. It is also misused in some sports to reduce cardiac frequency, contraction force and coronary flow [2]. The International Olympic Committee has taken propranolol as a doping substance and included it in the list of forbidden substances [3]. Owing to its therapeutical and pharmacological relevance, the rapid and accurate determination of propranolol in commercial formulations is necessary to control propranolol intake. A variety of analytic techniques, including fluorimetry [4,5], electrochemistry [6,7], electrochemiluminescence (ECL) [8] and highperformance liquid chromatography [9] have hitherto been utilized for the determination of propranolol. However, previous methods require the use of expensive instrumentation and lack sufficient sensitivity, and some of them involve long analysis times and tedious preliminary procedures such as pre-concentration in an organic solvent. Therefore, the development of high sensitivity, simple, rapid and cheap analytic method to determine propranolol in pharmaceutical preparations still has a great challenge. n
Corresponding author. Tel.: þ 86 591 22863264. E-mail address: [email protected] (Y. Qi).
http://dx.doi.org/10.1016/j.jlumin.2015.11.013 0022-2313/& 2015 Elsevier B.V. All rights reserved.
Chemiluminescence (CL) is known as a powerful and important analytical technique, because of its extremely high sensitivity along with its other advantages, such as simple instrumentation, wide calibration ranges, and suitability for miniaturization in analytical chemistry [10–15]. On the other hand, metal nanoparticles, especially precious metal nanoparticles have attracted attention in the last few years, owing to their unique structure, electronic, magnetic, optical, and catalytic properties, which have made them a very attractive material for biosensor systems and bioassays. Recently, precious metal nanoparticles also participate in the CL reaction as a catalyst, reductant, luminophor, and energy acceptor [16–19], which improve the performance of the CL system and expand its application. At the same time, precious metal nanoparticles CL assay has also been used to the determination of various drugs. Some organic medicines like isoniazid, nitrofurans and bisphenol A were determined based on silver nanoparticles (AgNPs)-catalyzed CL assay [20–22]. In order to obtain the stronger CL signal, gold nanoparticles (AuNPs) of various shapes like gold nanorod and triangular AuNPs have been used for CL analysis of organic medicament [23–25]. In addition, Au/Ag alloy nanoparticles have also been found to have catalytic ability for CL reaction, and the determination of vitamin C and anticancer drug flutamide have been developed [26,27]. Other metal nanoparticles (such as cupric oxide nanoparticles [28] and iron nanoparticles [29]) also were successively introduced to the research of CL analysis of drug. However, the preparation of these above nanoparticles required laborious procedures such as refluxing and wash, constant temperature overnight, and stabilization by the polyethylene glycol (PEG),
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
which was much more complex than that of spherical AuNPs. To the best of our knowledge, no CL analysis for the detection of propranolol involved spherical AuNPs was reported. In fact, the morphology of spherical AuNPs directly affects their catalytic performance for CL reaction. Our previous works [30–33] found that aggregated AuNPs could display stronger catalytic activity on luminol CL reaction than the dispersed AuNPs because of the decrease of the surface negative charge density of AuNPs. It was found that besides the shape and size, surface charge property of AuNPs was the important influence factor for their catalytic activity on luminol CL reaction. Additionally, AuNPs could interact with propranolol strongly and lead to AuNPs’s aggregation [34]. It is possible that during the interaction of AuNPs with propranolol, surface charge property of AuNPs would be changed. Therefore, AuNPs's aggregation induced by propranolol offers the possibility of applying this phenomenon to direct AuNPs–CL assay propranolol. The applicability of aggregated AuNPs used in the direct AuNPs–CL assay propranolol depends on whether or not the aggregated AuNPs induced by propranolol show different catalytic activity for the CL reaction. In this work, the catalytic ability of aggregated AuNPs induced by propranolol on the luminol CL system was first studied. It was found that aggregated AuNPs induced by propranolol could also enhance the luminol CL signal in comparison with dispersed AuNPs. Based on this finding, the luminol–H2O2–aggregated AuNPs CL system was utilized to develop a new and simple AuNPs–CL protocol for the determination of propranolol. A schematic diagram of this method is shown in Scheme 1. In the absence of propranolol, AuNPs had high negative charge density and was monodispersed, and could induce a weak CL signal of luminol–H2O2 system. In the presence of propranolol, the interaction of propranolol and AuNPs could reduce surface negative charge density of AuNPs and cause AuNPs's aggregation, and initiate a strong CL signal.
2. Experimental 2.1. Chemical and reagents Propranolol was purchased from National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China).
O
N H OH
. HCl Fig. 1. Structure of propranolol hydrochloride.
239
The tablets containing propranolol was purchased from Lijun Pharmaceutical Co., Ltd. (Xi'an, China). Chloroauric acid (HAuCl4 4H2O) was purchased from Sinopharm Chemical Reagent Company (Shanghai, China). Sodium citrate and sodium hydroborate (NaBH4) were purchased from Tianjing Chemical Reagent Company (Tianjing, China). Other reagents and chemicals were of analytical grade and used without further purification. Doubly distilled and deionized water was used throughout. Luminol stock solution (2.5 10 2 M) was prepared by dissolving 4.43 g luminol in 20 mL of 0.10 M NaOH and then diluting to 1 L with water. The luminol solution was stored in dark for one week prior to use ensured that the reagent property had stabilized. Working solutions of luminol were prepared by diluting the stock solution. Working solutions of H2O2 were prepared fresh daily from 30% (w/w) H2O2. 2.2. Apparatus The CL intensity was measured and recorded on an IFFL-D chemiluminescence analyzer (Xi'an Ruimai Electronic Sci. Tech. Co. Ltd., Xi'an, China). UV–visible adsorption spectra were recorded on a Hitachi U-3900H UV–vis spectrophotometer. The transmission electron microscopy (TEM) images of AuNPs were taken by using a JEM-2100 TEM (Japan Electronics Co., Ltd.). The determination of zeta potential was carried out by Malvern Zetasizer 2000. The pH detections were carried out on a PHS-3E analyzer (Jiangsu, China). 2.3. Synthesis of AuNPs All glassware used in these preparations was thoroughly cleaned in aqua regia (1:3 HNO3–HCl), rinsed in doubly distilled water, and oven-dried prior to use. 2.6 nm AuNPs were prepared by hydroborate reduction method [35]. Briefly, 100 mL of 0.01% HAuCl4 solution under vigorous stirring was mixed with 1 mL of 1% trisodium citrate and 1 mL of 0.075% NaBH4/1% trisodium citrate solution at room temperature. The mixed solution was stirred for 30 min and then stored in 4 °C refrigerator before use. 6 nm AuNPs were also synthesized by hydroborate reduction method [35]. In brief, 0.40 mL of 1% trisodium citrate solution was added into 100 mL of 0.01% HAuCl4 solution and stirred for 1 min. Then 0.15 mL of 0.075% NaBH4/1% trisodium citrate solution was added and stirred for another 15 min and then stored in 4 °C refrigerator before use. AuNPs with the diameters of 16 nm and 25 nm were synthesized by sodium citrate reduction method [36,37]. For the synthesis of 16 nm AuNPs, 100 mL of 0.01% HAuCl4 solution was heated to boil. 2 mL of 1% trisodium citrate solution was rapidly added into HAuCl4 solution with vigorously stirring and remained at boiling for 15 min. The heating source was then removed and the solution was continuously stirred for another 15 min. The procedures for the synthesis of 25 nm AuNPs were similar to that of 16 nm AuNPs by decreasing the added volume of 1% trisodium
Scheme 1. Schematic representation of the proposed CL assay for propranolol.
240
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
citrate from 2.0 mL to 1.5 mL. The as-prepared AuNPs solutions were stored in a 4 °C refrigerator. 2.4. Procedure for the CL detection of propranolol The whole procedure could be divided into two stages: (1) the interaction between propranolol and AuNPs, and (2) CL detection. A standard CL detection of propranolol was realized as following procedure: first, 200 mL AuNPs solution was mixed with 200 mL propranolol solutions with different concentrations, the mixed solution was incubated for 3 min at the room temperature, leading to the aggregation of AuNPs. Second, after the interaction between propranolol and AuNPs, a 100 μL above AuNPs/propranolol solution was pipetted into a 40 14 mm2 quartz tube (used as CL reactor), then 200 μL luminol–H2O2 CL solution (the volume ratio of 5 10 4 M luminol and 5.0 10 2 M H2O2 was 2:1) was injected, and the CL signal was measured and recorded with the IFFL-D Chemiluminescence Analyzer. The concentration of propranolol was quantified by the CL intensity. The CL experiments in this work were not consecutive measurements.
3. Results and discussion 3.1. Change of 6 nm AuNPs induced by propranolol The prepared AuNPs (E6 nm) in aqueous solution are stable, as a result of the electrostatic repulsion of the negative capping agent (e.g. citrate ion) against the van der Waals attraction between AuNPs [38]. The AuNPs have a surface plasma resonance (SPR) absorption peak at about λ ¼520 nm and appear pink [39]. Propranolol could interact readily with AuNPs and induce the aggregation of AuNPs [34]. The aggregated AuNPs have a broad SPR absorption in the range of λ ¼ 550–850 nm. UV/vis spectroscopy was used to explore the change of AuNPs state induced by propranolol in this system. As shown in Fig. 2A, the AuNPs in the absence of propranolol have a SPR absorption peak at λ ¼520 nm; after the action of propranolol, the absorption spectrum for the AuNPs is broad and featureless, which indicates that the aggregation of AuNPs appears. The results were consistent with the transmission electron microscopy (TEM) images (Fig. 2B). The mechanism behind the phenomenon lies in the interaction between propranolol and AuNPs. It is known that SPR is the coherent excitation of all the ‘‘free’’ electrons within the conduction band, leading to an inphase oscillation. In fact, SPR of AuNPs mainly depends on the dipole moment of particles; that is to say, it is closely related to its surface states and the substance adsorbed on the surface of particles [40,41]. In addition, it was reported that citrate ions on the surface of AuNPs could be readily replaced by – NH– ligand in organic compounds [42]. So, in the presence of propranolol, citrate ions on the surface of AuNPs are replaced by the –NH– group in the structure of propranolol. The replacement of citrate ions with propranolol reduced the negative charge density on the surfaces of AuNPs and resulted in the loss of negative charge repulsion of AuNPs [41]. Consequently, the propranolol induced the aggregation of AuNPs. 3.2. Enhancement of the catalytic activity of AuNPs after the action of propranolol The luminol–H2O2 system can be effectively catalyzed by some metal nanoparticles. Cui and co-workers first discovered the catalytic activity of AuNPs in the luminol–H2O2 system, and found that the size of AuNPs was an important influence factor for their catalytic activity [16]. In our previous study, the electron density in the conduction bands of AuNPs and the surface-charge density of
Fig. 2. (A) UV–visible absorption spectra of AuNPs in the absence and presence of propranolol and (B) TEM images of 6 nm. AuNPs (a), and AuNPs after the adding of propranolol (b).
AuNPs were found to also have a significant influence on the catalytic activity of AuNPs in luminol–H2O2–AuNPs CL system [31– 33]. Hence, the catalytic activity of AuNPs must be relevant to the substance adsorbed on their surface, because the adsorbed substance can directly alter the size, morphology, and surface state of AuNPs, and further affect their microcosmic property such as conduction bands electron density and surface charge density. In the interaction between propranolol and AuNP, citrate ions on the surface of AuNPs were replaced by the –NH– group in the structure of propranolol so that AuNPs losed strong electrostatic repulsion of the electronegative capping agent citrate ion, and the morphology of AuNPs was transformed from dispersed state to aggregated state. We investigated the effect of propranolol on the catalytic activity of AuNPs in the luminol–H2O2 system. The CL behavior of the luminol–H2O2–AuNPs system was determined as the surface of AuNPs (E6 nm) was surrounded by propranolol. As shown in Fig. 3, propranolol itself could slightly inhibit the CL signal of luminol–H2O2 reaction in the absence of AuNPs, probably because that propranolol competed with luminol for H2O2 and the amount of the oxidant reacting with luminol was reduced. It also can be found from Fig. 3 that the AuNPs showed a certain degree of catalytic activity for the luminol–H2O2 system before adding propranolol. However, it is interesting to find that the aggregated AuNPs showed a rather strong catalytic activity, more than the dispersed AuNPs, after the introduction of propranolol in luminol–H2O2 system. Based on our previous study [30–33], the catalytic activity of AuNPs for luminol–H2O2 system may be influenced by the electron density in the conduction bands of AuNPs and the surface-charge density of AuNPs, indicating that more than one parameter was playing its sole to influence the catalytic activity of AuNPs. It is considered that higher electron density in the conduction bands would be favorable for the particle-mediated electron transfer processes and lead to higher catalytic activity [33]. The strong electric charge accumulation and oscillation effects occured in nanoparticles' specific sites would lead to the enhancement of SPR absorption, and SPR absorption
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
241
According to the above proposed mechanism for AuNPs catalytic activity enhancement, we further speculated that the cationic AuNPs with higher zeta potential value would show a higher catalytic activity than the anionic AuNPs, because the anionic HO2 (or anionic luminol) can easily interact with cationic AuNPs. To validate the scenario, we prepared amine modified cationic AuNPs (the preparation procedure is presented in Supporting information) and detected its zeta potential [43]. Zeta potential of the cationic AuNPs was þ32.6 mV. Indeed, this cationic AuNPs showed superstrong catalytic property, which was far more than the anionic AuNPs (Fig. 3). Therefore, we reasoned that propranolol could result in a remarkable increase of catalytic activity of AuNPs on the luminol–H2O2 CL system mainly because of the change of the surface charge property of AuNPs. Fig. 3. Effects of 6 nm AuNPs and cationic AuNPs on the luminol–H2O2 CL reaction. Conditions: luminol, 5 10 4 M; H2O2, 5.0 10 2 M.
intensity from UV–vis absorption spectra is considered to be able to indicate the electron density in the conduction bands of nanoparticles [40]. However, UV–vis absorption spectra of aggregated AuNPs in the presence of propranolol did not rise but decreased slightly when compared with the dispersed AuNPs (Fig. 2A), indicating that the electron density in the conduction bands of aggregated AuNPs induced by propranolol was not higher than that of dispersed AuNPs. Therefore, in the luminol–H2O2–AuNPs– propranolol CL catalytic system, the electron density in the conduction bands of AuNPs was not supposed to be the main influence factor, there must be other ones that played their roles. We reasoned that the enhancement effect of the aggregated AuNPs induced by propranolol may be attributed to the change of the AuNPs surface-charge density. Analysis results revealed that the zeta potentials of the dispersed AuNPs (E6 nm) and the aggregated AuNPs (E 6 nm) were 40.8 and þ0.28 mV, respectively. It is clear that the surface negative charge density of AuNP is greatly decreased, and charge property is actually changed from negative charge to positive charge after the aggregation of AuNP induced by propranolol. For the luminol–H2O2 CL system, the optimized pH conditions are generally about 11–12. The hydroperoxide ion (HO2 ), easily formed in strong alkaline medium, has an acid–base equilibrium (pKa ¼ 11.7) with H2O2. Similarly, the luminol anion is the main molecular form of luminol in strong alkaline medium. The anionic HO2 (or anionic luminol) does not easily interact with the anionic AuNPs whose surface is surrounded by citrate ions due to the electrostatic repulsion. The dispersed AuNPs, which have a high surface negative charge density ( 40.8 mV), have a rather low catalytic effect on the luminol–H2O2 CL reaction. The replacement of citrate ions on the surface of AuNPs by the –NH– group in the structure of propranolol loses its ability to protect the AuNPs. The –NH– group can screen the repulsion between the negatively charged AuNPs, and the zeta potential of AuNPs after propranolol's action was changed to be þ0.28 mV, which lead to the aggregation of the AuNPs. This is consistent with the previous reports in which AuNPs aggregated when its zeta potential Z 30 mV and r þ 30 mV [41]. The aggregated AuNPs with zeta potential þ0.28 mV can more easily interact with the anionic HO2 (or anionic luminol), resulting in a higher catalytic effect on the luminol–H2O2 reaction (Fig. 3). It is clear that the conversion of aggregation state before and after AuNPs–propranolol interaction would be easily distinguishable by a CL analysis of the luminol– H2O2 CL system. Hence, we reasoned that the change of the surface charge density of AuNPs resulted in the enhanced catalysis of the aggregated AuNPs.
3.3. Optimization of assay conditions Based on the principle of the AuNPs CL sensing for propranolol, there are two main actions: the AuNPs–propranolol interaction and AuNPs' catalysis for the luminol–H2O2 CL reaction. Two strategies were developed for the analysis: Strategy 1: the AuNPs and the propranolol solution were first mixed and allowed to incubate for a set period, and then the luminol/H2O2 mixed solution was injected into the AuNPs solution. Strategy 2: the AuNPs, propranolol and luminol solution were first mixed in reactor, and then the H2O2 solution was injected into the mixed solution. Analysis of the experimental results revealed that the sensitivity of AuNPs CL method in Strategy 1 was higher than that of Strategy 2. In this AuNPs CL method for propranolol, the AuNPs–propranolol interaction is the replacement process of substance adsorbed on the surface of particles and is the key factor for the detection of propranolol. In Strategy 1, the replacement is completely separate from detection so that it can be done under optimal conditions. In Strategy 2, luminol might influence the ion replacement process. This may be the reason why the sensitivity in Strategy 2 is lower. Moreover, it is well known that the luminol–H2O2 CL reaction is very slow and weak CL reaction in the absence of a catalyst. Thus, we chose Strategy 1 (shown in Scheme 1) as the analytical strategy for the assay. With a fixed strategy, the performance of the developed CL method is still strongly influenced by the assay conditions, such as, AuNPs size and concentration, and the CL reaction conditions. Different assay conditions were investigated in our studies. The size and concentration of AuNPs, the vital parameters for propranolol detection, were explored. In this system, AuNPs are the signal element and the size of the AuNPs influences the propranolol–AuNP interaction. Simultaneously, the size of the AuNPs also affects the catalytic activity of AuNPs in the luminol–H2O2 CL reaction. The previous studies showed that in the small size range, the increasing size of the AuNPs resulted in an increase in catalytic activity [16]. For this CL method, the CL signal from the dispersed AuNPs is taken as the background. Therefore, the small-sized AuNPs should be used to achieve high sensitivity. As shown in Fig. 4A, all of the examined AuNPs had the enhancement on the CL reaction. The CL intensity increased with increasing particle size from 2.6 to 6 nm AuNPs. This might be attributed to Fermi level shift, which leads to an alteration of the energy gap for particlemediated electron-transfer processes [44]. For larger particles (from 6 to 25 nm diameter), the CL intensity decreased with increasing particle size, probably because that the particles of smaller size have higher numbers of active sites on their surfaces for a given amount of catalyst material, which lead to a higher rate of catalytic reaction [44]. Therefore, we used the 6 nm AuNPs in this CL method. The sensitivity of the CL method is also influenced by the AuNPs concentration. If the AuNPs concentration is too high, the system is not sensitive enough to detect small amounts
242
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
Fig. 4. Effects of reactant conditions on the CL intensity. (A) The size and concentration of AuNPs; reaction conditions: 5 10 4 M luminol, 5.0 10 2 M H2O2, pH 12.0. (B) Luminol concentration; reaction conditions: pH 12.0, 5.0 10 2 M H2O2, 1.6 10 4 M AuNPs (6 nm). (C) H2O2 concentration; reaction conditions: pH 12.0, 5 10 4 M luminol, 1.6 10 4 M AuNPs (6 nm). (D) pH ; reaction conditions: 5 10 4 M luminol, 5.0 10 2 M H2O2, (6 nm) 1.6 10 4 M AuNPs (6 nm). The concentration of propranolol in all reaction conditions was 1 10 8 g mL 1.
of propranolol and does not differentiate them from the background. From Fig. 4A, the CL intensity increased with increase of the concentration of 6 nm AuNPs solution up to 1.6 10 4 M. Above this concentration, the CL intensity decreased. The reason might be that AuNPs in high concentration undergone strong interactions among these particles and the CL energy transfer occurred [21]. So, in this system, we used 1.6 10 4 M of AuNPs (E 6 nm) for all experiments. Furthermore, we investigated the effect of the age of the AuNPs. For the same concentration of propranolol, the signal did not change for the fresh AuNPs over one week, but the sensitivity decreased markedly if the AuNPs were stored for a month or more. The reason is that the AuNPs themselves aggregate during the stored time. For this reason we prepared very dilute AuNPs solutions on a weekly basis for our experiments. The important experimental parameters influencing the CL reaction of luminol–H2O2–6 nm AuNPs, including the concentrations of luminol and H2O2, and media pH, were optimized. Fig. 4B showed the effect of luminol concentration on the CL reaction. It was found that in the range of 0.01–0.5 mM the CL intensity increased with increasing luminol concentration. When the luminol concentration was higher than 0.5 mM, the CL intensity decreased. The possible reason is that luminol of high concentration could produce self-absorption of the emitted radiation and decrease the CL intensity [28]. In addition, it was also reported that the increase of ionic strength could cause the CL decrease [45]. Because the luminol solution was prepared by dissolving luminol in NaOH solution, ionic strength of the system increased with the
increase of luminol concentration, leading to the decrease of CL intensity. The effect of the H2O2 concentration on the CL was studied in the range of 0.01–200 mM (Fig. 4C), and the CL signal rose fast at first between 0.001 and 5 10 2 M, then very slowly, and remained almost constant above 5 10 2 M. The experimental results showed that the optimal pH for this CL system was 12.0 (Fig. 4D), which is in agreement with the results of previous studies [30,32]. 3.4. Analytical performance of this CL assay for propranolol Under the optimized conditions, experiments were carried out by adding increasing amounts of propranolol to the CL method to examine whether the CL change could be used for propranolol quantification. As shown in Fig. 5, the CL intensity increases with the increasing propranolol concentration. The CL intensity of this CL system was linear with the concentration of propranolol in the range from 8.2 10 11 to 8.6 10 8 g mL 1 (Fig. 6). The relative standard deviation (RSD) was 3.8% for 6.6 10 9 g mL 1 propranolol, calculated after studying six replicate injections of luminol– H2O2 CL reagents. The detection limit is an estimate of the concentration at which we can be fairly certain that the compound is present, concentrations below which may not be detected; for this experiment it was estimated to be 6.6 10 12 g mL 1 using 3σ. Compared with the previously reported results in Table 1, the increase in sensitivity of this system is 4 orders of magnitude more than that of the known CL method for the detection of propranolol [6], and the detection limit attained that reported for an ECL
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
sensor for propranolol [11]. The sensitivity of the proposed method is, therefore, feasible. In order to assess the possible application of the proposed method, the influence of commonly used excipients and additives in pharmaceutical formulations and potential interference in human urine samples was investigated for the determination of 8.2 10 11 g mL 1 propranolol. The tolerable limit of a foreign species was taken as a relative error of less than 5%. No interference could be found when the sample included up to 2000-fold K þ , NO3 ; SO24 ; CLO4 , Cl , Br , F , and 1000-fold NH4þ , glucose, maltose, ascorbic acid, citric acid, starch, sorbitol and sucrose, and 500-fold Mg2 þ , Al3 þ , CO23 , threonine, tryptophane, cyclodextrin and fructose, 100-fold Fe3 þ , Fe2 þ , Ca2 þ , Mn3 þ , methionine, alanine, thiourea, gelatine, urea and lactose. The selectivity of the proposed method was therefore evident. In the proposed method, the response of propranolol to CL signal was based on that in the interaction of propranolol and AuNPs, the replacement of citrate ions on AuNPs surface by the –NH– group in propranolol structure led to the change of AuNPs surface charge property, and AuNPs showed aggregation and an enhancement of catalytic activity. Actually, the difference in the change extent of AuNPs surface charge property could result in different aggregation and different enhancement of catalytic activity, which agreed with our previous research [32]. He et al. [46] developed Rayleigh light scattering (RLS) method for propranolol detection by AuNPs' aggregation induced by propranolol and the increasement of RLS intensity. In He's method, the interactions between AuNPs and many other doping agents (such as caffeine, furosemide, spironolactone, hydrochlorothiazide, methyltestosterone, testosterone, benzthiazide
Fig. 5. CL signals for triplicate measurement of AuNPs in different concentration propranolol. The concentrations of propranolol: (a) 0gmL 1, (b) 8.2 10 11gmL 1, (c) 2.6 10 10gmL 1, (d) 5.6 10 10gmL 1, (e) 8.9 10 10gmL 1, (f) 1.2 10 9gmL 1, (g) 6.6 10 9gmL 1, (h) 3.6 10 8g mL 1, (i) 6.2 10 8gmL 1, and (j) 8.6 10 8gmL 1. Conditions: luminol, 5 10 4M; H2O2, 5.0 10 2M.
243
and acetazolamide) could not lead to color change and AuNPs aggregation. In addition, they also found that other foreign substances such as metal ions, negative ions and amino acid also could not disturb the action between AuNPs and propranolol [46]. Hence, the possible reason for the good selectivity of the proposed method is that the interaction between foreign species and AuNPs is very weak, and the change extent of AuNPs surface charge property is very ‘micro’, so the catalytic activity enhancement is extremely weak when compared to propranolol. This result is similar to the good selectivity of He's Rayleigh light scattering (RLS) method for propranolol detection based on AuNPs aggregation [46]. 3.5. Determination of propranolol in tablets Commercial pharmaceutical propranolol samples (tablets) were analyzed to determine the substance in order to evaluate the validity of the proposed method. A tablet sample equivalent to approximately 10 mg of propranolol was weighed accurately and ground to a fine powder, and mixed homogeneously, and then dissolved in 10.0 mL of water. The resultant solution was filtered to remove any insoluble substances. The results are listed in Table 2. It can be seen that there was no significant difference between the results obtained by the proposed method and the Chinese pharmacopoeia method, by measurement of absorbance at 290 nm [47]. The feasibility of the CL method for the determination of propranolol is, therefore, evident. The method may be suitable for propranolol determination in medicine. 3.6. Determination of propranolol in spiked human urine To further test the possibility of applying this method to real biological samples, human urine samples added different concentrations of propranolol were analyzed. The urine samples were collected from different healthy volunteers. According to the references [48], known amount of propranolol standard solution was added into 1.0 mL of urine sample. The solution was gently vortex-mixed with 1.00 mL of 2% ZnSO4 solution and 1.00 mL of 1.8% Ba(OH)2 solution to remove possible reducing substances, and then centrifuged at 5000 r/min for 20 min. The supernatant was diluted to appropriate concentration. Blank experiment was also carried out with the same procedure without adding propranolol. The results are shown in Table 3. It could be seen that the recovery and precision of this method were satisfactory. Moreover, the sample in our method was pretreated by ZnSO4–Ba(OH)2 solution removing possible reducing substances and centrifugation to obtain supernatant, and process time is within a mere half-hour. Sample pretreatment in other methods need hydrochloric acid
Fig. 6. Calibration curve of CL intensity versus propranolol concentration. The concentrations of propranolol: (A) 8.2 10 11–1.2 10 9 g mL 1, (B) 1.2 10 9– 8.6 10 8 g mL 1.
244
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
Table 1 A comparison of various methods for the determination of propranolol. Analytical technique
Reagents used and comments
Analytical ranges (g mL 1)
Detection limit (g mL 1)
Reference
Fluorescence Fluorescence ECL
Amberlite XAD-7 as solid support at 20 °C Sodium dodecyl sulfate, using feed-forward neural networks
0–1 10 7 1.06 10 9–5.32 10 7 2.96 10 11–1.48 10 9
2 10 10 2.3 10 10 8.87 10 12
[5] [4] [8]
1.75 10 7–1 10 6 2.01 10 5–1.51 10 4 0–2.0 10 5 8.2 10 11–8.6 10 8 5.9 10 8–2.66 10 6 1.48 10 7–1.48 10 5 2.01 10 10–1.36 10 7
7 10 8 ─ 3.8 10 8 6.6 10 12 5.3 10 8 1.48 10 9 5.03 10 11
[12] [11] [10] This method [6] [7] [9]
CL CL CL CL Voltammetry Electrochemistry Chromatography
2þ RuðbpyÞ3 ,
graphene as modified material Acid potassium permanganate reaction The oxidation of propranolol by acidic potassium permanganate Pyrogallol oxidized by periodate AuNPs-catalyzed luminol reaction Cathodically pretreated borondoped diamond electrode Britton–Robinson solutions, pulse polarography pH 2.0–12.0 Solid phase extraction and detected by tandem mass spectrometry with a turbo ionspray interface
Acknowledgments
Table 2 Determination of propranolol in tablets (mg/tablet). Samples
Claimed content
Present method
RSD (n¼ 5)%
Pharmacopoeia method
RSD (n¼ 5)%
1 2 3
10 10 10
9.82 9.65 10.38
1.6 0.6 2.5
9.76 10.18 10.29
2.1 1.5 0.9
This work was supported financially by Program for New Century Excellent Talents in Fujian Province University, the Natural Science Foundation of Fujian Province of China (2014J01167 and 2015J01034) and the Scientific Research Foundation of Fujian University of Technology (GY-Z10054 and GY-Z10055).
Appendix A. Supplementary material
Table 3 Determination of propranolol in spiked human urine. Samples
Added (10 3 mg L 1)
Found (10 3 mg L 1)
RSD (n¼ 5)%
Recovery %
No. 1 No. 2 No. 3 No. 4 No. 5
0.00 2.00 4.00 6.00 8.00
0.00 1.98 4.18 5.75 7.68
– 1.6 2.8 2.5 3.2
– 99.0 104.5 95.8 96.0
processing for over 24 h, and vacuum evaporation to dryness at room temperature using a rotary evaporator, and then dissolving residue to get the sample solution. So, sample pretreatment of our methods is more easy and convenient than that of other methods.
4. Conclusions In summary, a novel and sensitive strategy to convert the AuNPs–propranolol interaction event into CL signals by employing unmodified AuNPs as signaling probes is proposed in this study. This strategy has several significant advantages: 1) the AuNPs does not need labeling or modifying, so that the affinity of the original AuNPs is not changed by a label, and the method is simple, cheap, and easy to operate. 2) The assay is homogenous and occurs in the liquid phase, which makes it easy to automate by standard robotic manipulation of microwell plates. 3) The assay avoids the separation and washing steps, and the whole detection can be completed in 30 min. 4) The AuNPs–propranolol interaction is separated from the detection so that the interaction and the detection could occur in their own optimal condition, respectively. So, it offers high sensitivity. In addition, given the simplicity and sensitivity of CL detection, this study holds great promise for the analysis of pharmaceutical compounds, and may pave a general way to the development of AuNPs-based CL methods for a broad range of analytes.
Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.jlumin.2015.11.013.
References [1] T.P. Ruiz, C.M. Lozano, V. Tomás, J. Carpena, Talanta 45 (1998) 969. [2] J.A. Murillo-Pulgarıń, A. Alanõń-Molina, P. FernańdezLopʹ ez, Anal. Chim. Acta 370 (1998) 9. [3] P. Valderrama, R.J. Poppi, Anal. Chim. Acta 651 (2009) 31. [4] T. Madrakian, A. Afkhami, M. Mohammadnejad, Talanta 78 (2009) 1051. [5] J.F. Fernańdez-Sańchez, A.S. Carretero, C. Cruces-Blanco, A. Fernańdez-Gutieŕrez, J. Pharm. Biomed. Anal. 31 (2003) 859. [6] E.R. Sartori, R.A. Medeiros, R.C. Rocha-Filho, O.F. Fatibello, Talanta 81 (2010) 1418. [7] M.A. El-Ries, M.M. Abou-Sekkina, A.A. Wassel, J. Pharm. Biomed. Anal. 30 (2002) 837. [8] H. Qi, C. Wang, R. Zou, L. Li, Anal. Methods 3 (2011) 446. [9] P. Partani, Y. Modhave, S. Gurule, A. Khuroo, T. Monif, J. Pharm. Biomed. Anal. 50 (2009) 966. [10] G.Z. Tsogas, D.V. Stergiou, A.G. Vlessidis, N.P. Evmiridis, Anal. Chim. Acta 541 (2005) 149. [11] K.L. Marques, J.L.M. Santos, J.L.F.C. Lima, J. Pharm. Biomed. Anal. 39 (2005) 886. ́ M.T.A. Pardo, Anal. Chim. Acta 488 (2003) 81. [12] A. Townshend, J.A.M. Pulgarın, [13] S. Zhao, X. Li, Y.M. Liu, Anal. Chem. 81 (2009) 3873. [14] Z. Wang, S.Y. Chin, C.D. Chin, J. Sarik, M. Harper, J. Justman, S.K. Sia, Anal. Chem. 82 (2010) 36. [15] C. Dodeigne, L. Thunus, R. Lejeune, Talanta 51 (2000) 415. [16] Z.F. Zhang, H. Cui, C.Z. Lai, L.J. Liu, Anal. Chem. 77 (2005) 3324. [17] C.F. Duan, H. Cui, Chem. Commun. 18 (2009) 2574. [18] S. Gupta, S. Huda, P.K. Kilpatrick, O.D. Velev, Anal. Chem. 79 (2007) 3810. [19] J.M. Lin, M.L. Liu, J. Phys. Chem. B 112 (2008) 7850. [20] B. Haghighi, S. Bozorgzadeh, Microchem. J. 95 (2010) 192. [21] X. Chen, C. Wang, X. Tan, J. Wang, Anal. Chim. Acta 689 (2011) 92. [22] W. Liu, J. Kou, X. Jiang, Z. Zhang, H. Qi, J. Lumin. 132 (2012) 1048. [23] J.X. Du, J. Quan, Y.D. Wang, Talanta 90 (2012) 117. [24] C. Lu, Q.Q. Li, S. Chen, L.X. Zhao, Z.X. Zheng, Talanta 85 (2011) 476. [25] Q.S. Chen, S.L. Bai, C. Lu, Talanta 89 (2012) 142. [26] M.J. Chaichi, S.N. Azizi, M. Heidarpour, Spectrochim. Acta Part A 116 (2013) 594. [27] M.J. Chaichin, S.O. Alijanpour, J. Lumin. 134 (2013) 195. [28] W. Chen, L. Hong, A.L. Liu, J.Q. Liu, X.H. Lin, X.H. Xia, Talanta 99 (2012) 643. [29] B. Rezaei, A.A. Ensafi, L. Zarei, Spectrochim. Acta Part A 90 (2012) 223. [30] Y. Qi, B. Li, Chem. Eur. J. 17 (2011) 1642. [31] Y. Qi, B. Li, Spectrochim. Acta Part A 111 (2013) 1. [32] Y. Qi, B. Li, Z. Zhang, Biosens. Bioelectron. 24 (2009) 3581. [33] Y. Qi, F.R. Xiu, B. Li, Anal. Biochem. 449 (2014) 1. [34] R. Stiufiuc, C. Iacovita, G. Stiufiuc, E. Bodoki, V. Chis, C.M. Lucaciu, Phys. Chem. Chem. Phys. 17 (2015) 1281.
Y. Qi, F.-R. Xiu / Journal of Luminescence 171 (2016) 238–245
[35] [36] [37] [38] [39] [40] [41] [42]
K.R. Brown, A.P. Fox, M.J. Natan, J. Am. Chem. Soc. 118 (1996) 1154. G. Frens, Nat. Phys. Sci. 241 (1973) 20. Z.F. Zhang, H. Cui, M.J. Shi, Phys. Chem. Chem. Phys. 8 (2006) 1017. K.C. Grabar, R.G. Freeman, M.B. Hommer, M.J. Natan, Anal. Chem. 67 (1995) 735. H. Li, L.J. Rothberg, J. Am. Chem. Soc. 126 (2004) 10958. S. Link, M.A. El-sayed, Int. Rev. Phys. Chem. 19 (2000) 409. C. Kyungnam, L. Yunhee, L.H. Chang, L. Kangtaek, K. Youngmin, C. Hyoungwoo, R.D. Pan, L.Y. So, J.W. Sang, J. Phys. Chem. C 112 (2008) 8629. V. Selvaraj, M. Alagar, Int. J. Pharm. 337 (2007) 275.
245
[43] T. Niidome, K. Nakashima, H. Takahashi, Y. Niidome, Chem. Commun. 17 (2004) 1978. [44] R.K. Sharma, P. Sharma, A. Maitra, J. Colloid Interface Sci. 265 (2003) 134. [45] M. Yang, R. Liu, Y. Xu, Y. Zou, X. Song, Biosens. Bioelectron. 22 (2007) 871. [46] H.Y. Duan, F. Chen, X.P. Ai, Z.K. He, Chin. Chem. Lett. 16 (2005) 947. [47] Chinese Pharmacopoeia Commission, The Pharmacopoeia of People's Republic of China (Part II), Chemical Industry Press, Beijing (2000), p. 683. [48] D.C. Williams, G.F. Huff, W.R. Seltz, Clin. Chem. 22 (1976) 372.