Determination of dexamethasone by flow-injection chemiluminescence method using capped CdS quantum dots

Accepted Manuscript Determination of dexamethasone by flow-injection chemiluminescence method using capped CdS quantum dots Alireza Khataee, Aliyeh Hasanzadeh, Roya Lotfi, Rahmatollah Pourata, Sang Woo Joo PII: DOI: Reference:

S1386-1425(15)00636-8 http://dx.doi.org/10.1016/j.saa.2015.05.047 SAA 13715

To appear in:

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Received Date: Revised Date: Accepted Date:

18 March 2015 14 May 2015 17 May 2015

Please cite this article as: A. Khataee, A. Hasanzadeh, R. Lotfi, R. Pourata, S.W. Joo, Determination of dexamethasone by flow-injection chemiluminescence method using capped CdS quantum dots, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2015), doi: http://dx.doi.org/10.1016/j.saa.2015.05.047

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Determination of dexamethasone by flow-injection chemiluminescence method using capped CdS quantum dots

Alireza Khataee,a,* Aliyeh Hasanzadeh,a Roya Lotfi,a Rahmatollah Pourata,b Sang Woo Joo c,**

a

Research Laboratory of Advanced Water and Wastewater Treatment Processes, Department

of Applied Chemistry, Faculty of Chemistry, University of Tabriz, 51666-16471 Tabriz, Iran b

Department of Chemistry, Faculty of Science, University of Zanjan, 45371-38791 Zanjan,

Iran c

School of Mechanical Engineering, Yeungnam University, 712–749 Gyeongsan, South

Korea

*

Corresponding author (communicator)

E–mail address: [email protected] ([email protected]) Tel.: +98 41 33393165; Fax: +98 41 33340191

**

Corresponding author

E–mail address: [email protected] Tel: +82 53 810 1456

1

Abstract L-cysteine capped CdS quantum dots (QDs) were synthesized through a facile hydrothermal method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL) and UV-Vis spectroscopy. The light emitted from KMnO4–L-cysteine capped CdS QDs reaction in acidic medium was applied as a simple and sensitive chemiluminescence (CL) system for determination of dexamethasone. The CL intensity of KMnO4–L-cysteine capped CdS QDs CL system was remarkably enhanced in the presence of dexamethasone. Under optimum experimental conditions, the enhanced CL intensity was related to dexamethasone concentration in the range of 0.004 to 25.0 mg L−1, with the detection limit (3σ) of 0.0013 mg L−1. The analytical applicability of the proposed CL system was assessed by determining dexamethasone in spiked environmental water samples and pharmaceutical formulation. The analytical performances of proposed flow– injection CL method for the determination of dexamethasone were compared with those obtained by corona discharge ionization ion mobility spectrometry (CD-IMS) method. The proposed CL system exhibits a higher sensitivity and precision than the CD-IMS method for the determination of dexamethasone.

Keywords: CdS quantum dots; Chemiluminescence; Dexamethasone; Flow injection; Nanocatalyst.

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1. Introduction Dexamethasone is a potent synthetic derivative of the glucocorticoid hydrocortisone [1]. It is frequently used in clinical practice as an anti-inflammatory and immunosuppressive agent for the treatment of allergy, inflammation, congenital adrenal hyperplasia, and autoimmune conditions [1, 2]. These drugs have been added in to the list of banned drugs because of misusing as doping agents in sports as cycling and horse racing to enhance the performance [3]. Therefore, development of sensitive and simple analytical approaches to determine dexamethasone in many fields, including doping control, and pharmacokinetic study is of importance. Moreover, the occurrence of different pharmaceuticals in the aquatic environment results from direct release from production facilities, human and animal excretion of unchanged pharmaceuticals, and the metabolites and incorrect disposal of expired medicines [4, 5]. In past decades, trace levels of these compounds have been detected in water resources. This is a major concern and a potential threat to human health, as well a threat to aquatic organisms [6]. According to the aforementioned considerations, the detection of dexamethasone in environmental water samples is very important. As a result of the widespread use of dexamethasone, several analytical techniques have been exploited for the determination of dexamethasone in recent years, including liquid chromatography– tandem mass spectrometry (LC-MS-MS) [7, 8] high performance liquid chromatography (HPLC) [9-12] Spectrophotometry [1], electrochemical [3], and chemiluminescence (CL) [2, 12, 13]. Although the chromatography methods are used for the determination of dexamethasone in the diverse matrix, these methods suffer from some imperfections such as expensive instrumentation, tedious extraction procedures, the need for toxic and costly organic

solvents,

derivatization,

and

considerable

processing

time

Spectrophotometric methods have low sensitivity and a high detection limit [15].

3

[3,

14].

CL has received considerable attention as an efficient detection tool in wide variety of analytical applications, due to their simplicity of operation, rapid response, high sensitivity, wide dynamic range, and without disturbances and light-scattering [16]. In recent decades, the flow–injection CL method has attracted the attention of researchers as a powerful tool in many basic research and practical applications including clinical diagnosis [17], environmental monitoring [15, 18], and pharmaceutical analysis [19]. Recent advances in the CL systems based on colloid semiconductor nanocrystals and quantum dots (QDs) have attracted an increased attention because of their good chemical stability, unique sizedependent optical and electronic properties [20]. Most CL systems have weak luminescence intensity due to the low quantum yield. In this respect, fluorescent compounds such as QDs with high quantum efficiency can improve this weak intensity [21]. Therefore, it would be more importance to investigate the novel CL behavior of QDs for the developing novel CL sensors [20, 22]. Li et al. [23] and Wang et al. [24] pointed out that CdTe and CdS QDs could be directly oxidized by H2O2 in basic conditions. In another work, Li et al. [25] reported that CdTe QDs modified with three different thioalkyl acids (mercaptoacetic acid, cysteine, and glutathione) could be directly oxidized by K3Fe(CN)6 generated CL emission in alkaline media. It should be pointed out that the quantum yield of QDs–H2O2 CL systems is considerably low in comparison with the traditional CL systems such as luminol-oxidant systems [20]. Furthermore, in the reported QDs–H2O2 CL systems, high concentration of H2O2 (1 mol L-1 [23] or 0.8 mol L-1 [24]) was utilized as the CL oxidant. The decomposition of high concentration of H2O2 is very fast in the strong basic media, which would produce unstable CL signals [26]. These shortcomings may impede further extension of applications of QDs– H2O2 CL systems. Accordingly, optimizing CL reaction condition is of importance to improve the analytical performance of QDs CL systems.

4

Regarding to our knowledge, there is no previous report pointed out the enhancing efficiency of dexamethasone on KMnO4–L-cysteine capped CdS QDs CL system in the acidic solution. In the present work, a strong CL signal has been observed through adding dexamethasone to the KMnO4–L-cysteine capped CdS QDs system and the resultant increase in the CL intensity is proportional to its concentration. Based on this phenomenon, a sensitive and simple flow–injection CL method has been developed for the determination of dexamethasone in spiked environmental water samples and pharmaceutical formulation. The possible mechanism of CdS QDs CL system was studied. Also, the obtained analytical results from the proposed CL and corona discharge ionization ion mobility spectrometry (CD-IMS) methods for the determination of dexamethasone were compared.

2. Materials and methods 2.1. Materials and solutions All the chemicals and reagents used were of analytical reagent grade and purchased from Merck Co. (Germany). Dexamethasone was supplied by Aburaihan pharmaceutical Co. (Tehran, Iran). Doubly distilled water was used overall the experiments. A 100 mg L−1 stock standard solution of dexamethasone was freshly made by dissolving 10 mg dexamethasone in 100 mL of doubly distilled water, which was then stored at 4 °C in a refrigerator and kept away from light.

2.2. Apparatus The CL signals produced from the CL reaction in the flow cell were detected with a FB12 luminometer (Berthold Detection Systems, Germany). The output from the luminometer was captured by the computer for data acquisition. Ultraviolet-visible (UV-Vis) spectra of samples were recorded on a UV–Vis spectrophotometer (WPA Lightwave S2000, England). 5

The X-ray diffraction (XRD) patterns were recorded to determine the crystal phase composition of synthesized CdS QDs using a Siemens X-ray diffractmeter D5000 (USA), with CuKα radiation source of 1.54065 Å, the accelerating voltage of 40 kV and emission current of 30 mA. The average crystalline size of the samples was calculated according to the Debye–Scherrer formula [27]. The surface morphology and size of the synthesized QDs samples were characterized by scanning electron microscopy (SEM) via Mira3 FEG SEM (Tescan, Czech Republic). Moreover, the obtained SEM image was analyzed using Microstructural Image Processing (MIP) software (Nahamin Pardazan Asia Co., Iran) to determine the particle size distribution of the samples. Fourier transform infrared (FT-IR) spectra were recorded with an IR-spectrometer (Tensor 27, Bruker, Germany). The photoluminescence spectra were measured on a spectrofluorometer (FP-6200, Jasco, Japan). Ion mobility spectrometry (IMS) apparatus (model 200, TOF Tech. Pars Co., Iran) with the corona discharge ionization source in the positive mode were used in this study. This instrument consisted of various parts such as IMS cell, a thermostatic oven, a needle for generating the corona, power supplies, a pulse generator, an analog-to-digital converter (PicoScope, UK), and a computer for data processing. The IMS cell includes ionization and drift regions separated by shutter grid. A Faraday cup detector was applied for ion current collection.

2.3. Procedures for chemiluminescence assay Figure 1 depicts a schematic diagram of the laboratory-made flow–injection CL detection system utilized in this work. All the respective solutions were pumped into the flow cell using a peristaltic pump at an equal flow rate of 2.0 mL min-1 for each channel. A 100 µL of sample was injected into the flow cell by a six-port injection valve. Polytetrafluoroethylene tubes (1.0 mm internal diameter (i.d.)) were applied as a connection all the materials in the flow 6

system. As represented in Figure 1, the solution of acid (a), sample or standard solution of mixture of dexamethasone and L-cysteine capped CdS QDs (b), doubly distilled water as the carrier (c) and KMnO4 solution (d) were continuously pumped. The solutions (a) and (b) were mixed when passed through a mixing tube (silicon tubing, 1.0 mm i.d.). Then in the sample injection step, the mixture was injected into the carrier stream and combined with KMnO4 stream via a Y-piece. Eventually, the mixture was introduced into the flow cell to generate CL emissions. Data acquisition was carried out on a computer connected to the luminometer. The measurement of dexamethasone was carried out based on the enhancement of CL intensity, calculated as ∆I=I0–Is, where I0 and Is define the CL intensity in the absence and presence of dexamethasone, respectively.

2.4. Synthesis of L-cysteine capped CdS QDs Water-dispersible CdS QDs were prepared by a simple and direct hydrothermal method. In a typical procedure, appropriate amount of Cd(CH3COO)2.2H2O and Na2S were dissolved in distilled water. Afterwards, the pH value was adjusted to 10.0 with 1.0 M NaOH and then L-cysteine solution was added into the above solution. The typical molar ratio of Cd2+/S2-/ Lcysteine was 1:1.7:2.3. The resulting CdS QDs precursor was de-aerated under nitrogen atmosphere for 30 min and transferred into a 100 mL teflon lined autoclave. The autoclave was sealed, placed in an oven at 150 °C for designed time. Subsequently, absolute ethanol was used to precipitate the L-cysteine capped CdS QDs. The obtained samples were precipitated absolute ethanol and washed with distilled water several times to eliminate contaminants, and eventually vacuum dried at 40 °C for 5 h.

2.5. Pre-treatment of real sample solutions before assay

7

Ten commercial tablets containing dexamethasone were powdered and blended in a mortar. Then, the equivalent of 10 mg of dexamethasone, was weighed and dissolved in doubly distilled water, and the resulting solution was filtered with Whatman No. 42 filter paper. After transforming the filtered solution to a volumetric flask, 100 mg L−1 dexamethasone aqueous solution was obtained by diluting with doubly distilled water. Using standard methods, tap and ground water samples were freshly gathered into precleaned polyethylene flasks [15]. Collected water samples were immediately filtered via polyamide membrane filters with a 0.45 µm pore size to remove suspended solid matter, and were maintained in a dark place at 4 °C. Before analysis, 10 mL water samples were spiked with a certain volume of dexamethasone standard solutions (100 mg L-1) and diluted to 25 mL with doubly distilled water, in order to achieve the desired concentration of dexamethasone. To eliminate metal cations in the water samples, mentioned solutions were passed through a packed column compacted with a strong cation-exchanging resin (Chelex 100) at a flow rate of 4 mL min-1. The collected solutions were used for the determination of dexamethasone concentration by general procedure and using standard addition method. Then, the same procedure was performed with dexamethasone-free water samples for the determination of the blank value.

3. Results and discussion 3.1. Optical characteristics of synthesized L-cysteine capped CdS QDs UV-Vis absorption and PL spectra were used to investigate the optical properties of synthesized quantum dots for different hydrothermal durations (1, 2, 3, 4, 5, and 6 h), as shown in Figures 2a and 2b, respectively. All samples indicate a well-defined absorption maximum of the first electronic transition (1sh-1 se), which is attributed to quantum confinement in the as-prepared CdS QDs [23, 25]. The absorption maximum (Figure 2a) and 8

the PL peak (Figure 2b) show a red-shift that corresponds to the growth of the particle diameter of the CdS QDs as a consequence of increased hydrothermal process times. Peng’s equation [28] was applied in order to calculate the particle diameter of the as-prepared CdS QDs as follows: D = (−6.6521 × 10 −8)λ3 + (1.9557 × 10−4)λ2 − (9.2352 × 10−2)λ + 13.29

(1)

where D (nm) and λ (nm) are the size of CdS QDs and the wavelength of the first excitonic absorption peak of the QDs, respectively. According to the calculation, the particle diameter of the as-prepared CdS QDs with 1, 2, 3, 4, 5 and 6 h heating times were obtained as 2.84, 3.28, 3.58, 4.07, 4.85 and 5.32 nm. Also, the optical direct band gap of the QDs plays a significant role in the CL reactions [20]. For this, the optical direct band gap values of the CdS QDs after different heating durations were measured from optical absorption spectra by using Tauc’s relation [29]: (Ahυ)2 = K(hυ–Eg)

(2)

where A, hν, K and Eg are the absorption coefficient, the photon energy (eV), a constant and the optical direct band gap, respectively. Extrapolating the linear region in a plot of (Ahυ)2 versus hυ gives the band gap energy of the CdS QDs. The optical band gap values for asprepared CdS QDs with 1, 2, 3, 4, 5 and 6 h heating times were obtained as 3.38, 3.23, 3.11, 2.96, 2.83 and 2.62 eV, respectively. All these values are higher than the band gap of bulk CdS having an absorption edge located at 515 nm (Eg = 2.42 eV) [28], which shows that the quantum confinement in all prepared samples [30]. Indeed, the Eg values of CdS QDs diminish with the increase in particles size of as-prepared CdS QDs, which is attributed to the quantum confinement effect [22].

9

3.2. Structural characteristics of synthesized L-cysteine capped CdS QDs X-ray diffraction patterns of L-cysteine capped CdS QDs obtained at the 6 h reaction time are depicted in Figure 3a, which used for clarifying the crystalline nature of as-prepared samples. As shown, the main dominant peaks of L-cysteine capped CdS QDs are represented at 2θ (scattering angle) values of 24.9°, 26.6°, 28.3°, 36.8°, 43.9°, 48.1° 52.1°, 58.6° and 67.1° corresponding to the reflection from (100), (002), (101), (102), (110), (103), (112), (202) and (203) crystal planes, respectively. The characteristic peaks of as-synthesized CdS QDs are in good agreement with those of the standard patterns of hexagonal wurtzite CdS (JCPDS 41-1049). In addition, as shown in Figure 3a, no peaks attributable to impurities and other phase were detected, thereby confirming the high purity of the as-prepared sample. According to the Debye–Scherrer formula [27], the average crystalline size of L-cysteine capped CdS QDs obtained at the 6 h reaction time was found to be about 5 nm, based on the sharpest peak (2θ of 28.3°). The morphology and particle size of L-cysteine capped CdS QDs synthesized at the 6 h reaction time were investigated by SEM analysis. The results are illustrated in Figures 3b. As shown, L-cysteine capped CdS QDs are spherical in shape, well-defined, and have good homogeneity. Additionally, the particle size distribution plot of QDs is presented in Figure 3c which is in the range of 5-9 nm, which is consistent with the XRD and optical results. In addition, FT-IR spectroscopy was performed in order to confirm the bonding of L-cysteine to the CdS QDs surface. Figure 3d represents the FT-IR spectra of free L-cysteine and Lcysteine capped CdS QDs. As shown in the figure, the IR absorption band arounds 1550 to 1600 cm−1 (sυ COO−), 1400 cm−1 (mυ COO−), and 3500 to 3000 cm−1 (mυ carboxylic acid O–H) show the presentation of carboxyl group. The peak around 2900 to 3420 cm−1 (mυ N– H) indicates –NH2 group and 600 to 800 cm−1 (wυ C–S) depict the C–S group, also the peak at 2550 to 2750 cm−1 (wυ S–H) exhibits –S–H group [25, 31, 32].On comparison of the two 10

spectra, we note that the stretching band of the thiol group (2550 to 2670 cm−1) is not observed in the spectrum for L-cysteine capped CdS QDs. This may be attributed to the formation of covalent bonds between the thiol group of L-cysteine and the surface of CdS QDs [32].

3.3. Direct chemiluminescence of L-cysteine capped CdS QDs The preliminary investigations demonstrated that KMnO4 in acidic aqueous medium is able to directly produce a CL emission from CdS QDs. The dynamic CL intensity-time profiles of KMnO4–L-cysteine capped CdS QDs CL reaction enhanced by dexamethasone are shown in Figure 4. The CL intensity of KMnO4–L-cysteine capped CdS QDs reaction in the absence of dexamethasone are shown in Figure 5, curve a. Blank experiments were performed in the presence of Cd(CH3COO)2 and Na2S solutions in the concentrations used for preparation of QDs. No CL emission was observed for these solutions. This confirms that the CL arises from L-cysteine capped CdS QDs. As presented in Figure 4, curve b, when 8.0 mg L-1 dexamethasone is added into the KMnO4–L-cysteine capped CdS QDs CL system, the CL intensity significantly increased. It reveals that aforementioned CL system can be used for the determination of dexamethasone. Furthermore, it should be noted that in the absence of the L-cysteine capped CdS QDs, there was no response from KMnO4–dexamethasone in acidic condition.

3.4. Optimization of the chemiluminescence reaction conditions In order to obtain reaction conditions on which dexamethasone has the maximum enhancement effect on the CL intensity of the system, the effect of chemical parameters including the particle size of the QDs and the concentrations of KMnO4, H2SO4, and Lcysteine capped CdS QDs in the presence of 3.0 mg L-1 dexamethasone, were investigated. In 11

this sense, the effect of the KMnO4 concentration on the ∆I of the CL system in the range of 0.01 to 0.4 mmol L–1 was investigated (Figure 5a). ∆I increased with the concentration of KMnO4 to 0.08 mmol L–1 and then decreased at high concentrations, probably because of non-radiative de-excitation pathways [33]. Also, this observation can be concluded based on the absorption of the emitted light by a high concentration of KMnO4 [34]. Thus, 0.08 mmol L–1 was taken as the optimum value of KMnO4 concentration. Different concentrations of H2SO4 in the range from 0.01 to 2.0 mol L−1 were examined. Figure 5b depicts that the highest ∆I was obtained at 1.0 mol L−1 of H2SO4 solution and then ∆I decreased at high H2SO4 concentration. This observation might be due to the fact that the QDs are destroyed in the highly acidic media [34]. So, 1.0 mol L−1 of H2SO4 was selected for the subsequent experiments. The CL emission intensity of QDs depends on particles sizes. Many reports have indicated the size-dependent optical property of QDs [20, 23]. Figure 5c reveals that ∆I increases with the increase in the particle size of the CdS QDs from 2.84 to 5.32 nm. With respect to the CL energy match theory, the energy band gap of QDs diminishes with an increase in particle size [22]. Therefore, the CL emission intensity increases with the decreasing band gaps, which leads to a faster electron injection to the surface states of QDs [20, 23]. Also, a more intensive CL emission can be produced when more of the chemical energy matches the excitation energy required [24]. The effect of the concentration of 5.32 nm L-cysteine capped CdS QDs solution on the value of ∆I was tested. The value of ∆I was enhanced considerably by increasing the CdS QDs concentration up to 0.7 mmol L-1. A further increase in CdS QDs concentration resulted in a gradual decline in ∆I (Figure 5d). This effect is attributed to the strong interactions among QDs in the dense solution and the light quenching. In addition, the chemical energy of

12

the CL system cannot sufficiently excite all QDs [20, 35]. So, 0.7 mmol L-1 of 5.32 nm Lcysteine capped CdS QDs was selected for further experimentation.

3.5. Possible chemiluminescence mechanism In order to elucidate the possible mechanism of the CL reactions, CL, PL, and UV–Vis analyses were performed. Generated emitting species in the KMnO4–L-cysteine capped CdS QDs–dexamethasone CL system were investigated with CL spectra by using a spectrofluorimeter with the xenon lamp turned off. The obtained CL spectra are shown in Figure 6. As illustrated in Figure 6, curve a, two emission bands are observed in the KMnO4– L-cysteine capped CdS QDs system. The first band is located around 520 nm, and is similar to the PL spectra of the L-cysteine capped CdS QDs (5.32 nm particle size) with an excitation wavelength of 375 nm (see Figure 2b). As a strong oxidizer, KMnO4 injects a hole into the 1sh quantum-confined orbital of CdS QDs to produce hole-injected CdS (h+1sh) QDs. Moreover, at temperatures above absolute zero, electrons can excite into the high energy levels [36, 37]. The injection of holes into the CdS QDs by KMnO4 enhances the holes in the CdS QDs. Excitons are generated at the time of the electron-hole pair recombination. When (CdS QDs)* returns to its ground state, CL emission occurs (Eqs. (3) and (4)) [20, 38]. The other emission band is a small emission band at the red end of the spectrum that is located near 725 nm. This matched with the emission from excited manganese (II) (Mn(II)*) (from 4

T1 to 6A1 transition) in most of the acidic permanganate CL systems, which has a broad CL

spectrum with a maximum near 734 ± 5 nm (Eq. (5)) [34]. On the other hand, KMnO4 oxidizes the L-cysteine to produce excited intermediate (L-cysteine*) when it interacts with the CdS QDs. Then, (CdS QDs)* are formed from a CL resonance energy transfer process between L-cysteine* as the donor and CdS QDs as the acceptor (Eqs. (6) and (7)) [25]. Finally, (CdS QDs)* return to the ground state that produced the CL emission (Eq. (4)). 13

Also, from Figure 6, curve b, it can be clearly seen that the maximum emission wavelength of the KMnO4–L-cysteine capped CdS QDs CL system in the presence of dexamethasone is also located at 520 nm, with enhanced CL emission at λmax=520 nm. This approves that the addition of dexamethasone in to the KMnO4–L-cysteine capped CdS QDs system cannot produce a new luminophore and the final emitter is again (CdS QDs)*. The enhancement of CL emission intensity in the presence of dexamethasone can be attributed to that, KMnO4 can oxidize dexamethasone that leading to the production of excited state oxidized dexamethasone (oxidized dexamethasone*). The (oxidized dexamethasone*) can transfer energy to the CdS QDs, When it returns to the state of ground, this leads to the production of more (CdS QDs)*, the more (CdS QDs)*return to the state of ground with enhanced CL phenomena [18, 39]. The reaction mechanism of KMnO4–L-cysteine capped CdS QDs in the presence of dexamethasone is proposed in Eqs. (8) and (9). Furthermore, Figure 7 depicts the UV–Vis absorption spectrum of the KMnO4–L-cysteine capped CdS QDs–dexamethasone system. It can be seen that absorption for KMnO4 (around 540 nm) gradually decreases with increased reaction time, which illustrates the consumption of KMnO4 during its CL reaction with L-cysteine capped CdS QDs and dexamethasone. Thus, the CL reaction can be illustrated in its simplest form as follows [25, 30]:

MnO −4 + CdS QDs + 8H + → Mn (II )* + (CdS QDs) ∗ + 4 H 2 O

(3)

( CdS QDs)

(4)

∗

→ CdS QDs + h υ ( λ max = 520 nm )

Mn ( II ) ∗ → M n ( II ) + h υ ( λ max ≅ 725 nm )

(5)

MnO −4 + L - cysteine + 8H + → Mn ( II) + L - cysteine ∗ + 4H 2 O

(6)

L - cysteine * + CdS QDs → L - cysteine + (CdS QDs) *

(7)

MnO4- + Dexamethasone + 8H+→ Mn(II) + (Oxidized dexamethasone)* + 4H2O

(8)

(Oxidized dexamethasone)* + CdS QDs → Oxidized dexamethasone + (CdS QDs)*

(9)

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3.6. Ion mobility spectrum of dexamethasone Figure 8 depicts the ion mobility spectrum of dexamethasone with the corona discharge ionization source. These spectra were taken under the optimized CD-IMS circumstances given in Table 1. The spectrum of dexamethasone shows two peaks in the region of 8 to 9 and 10 to 12 ms (Figure 8). The reactant ions of background involved of water clusters ions (H2O)nH+ are also illustrated in Figure 8. The main mechanism in the CD-IMS is the proton transfer reaction from the reactant ion to the substance [40]. The chemical structure of the product ions emerging from dexamethasone cannot be defined without mass spectrometer analysis. However, these peaks can be considered as the index peak for the determination of dexamethasone.

3.7. Analytical performance for dexamethasone determination Under the optimum conditions applied in the present study, the increase in the CL intensity of KMnO4–L-cysteine capped CdS QDs by dexamethasone is linear over the concentration range of 0.004 to 25.0 mg L−1. The linear regression equation is y= 1655.00 x + 385.45 (r2 = 0.995), where y is ∆I and x is the dexamethasone concentration in mg L−1. The limit of detection (LOD) (3σ) of the CL method was calculated to be 0.0013 mg L−1. The relative standard deviation (RSD%) is 1.68% for eleven replicate determinations of 5.0 mg L−1 dexamethasone. These results reveal that the proposed CL system has relatively high sensitivity, a wide linear range (about four order of magnitudes), and acceptable precision. The area under the CD-IMS peaks for dexamethasone was considered to be the response. Under optimized CD-IMS conditions, a linear calibration curve was obtained for dexamethasone over the concentration range of 2.0 to 30.0 mg L−1. The linear regression equation is y= 78.25 x + 38.52 (r2 = 0.993), where y is the CD-IMS response and x is the 15

dexamethasone concentration in mg L−1. The LOD of the this method was calculated to be 0.38 mg L−1 and the RSD% for the eleven determinations of 4.0 mg L-1 dexamethasone is 2.65%. Comparison of analytical performances such as LOD values, precision and recoveries of these two analytical methods indicates that the proposed CL system has higher sensitivity and precision than the CD-IMS method for the determination of dexamethasone. Moreover, figures of merit of the proposed methods were compared with those of some previously reported works for determination of dexamethasone (see Table 2). It is worthy to mention that in comparison with most techniques used in the determination of dexamethasone, the proposed CL system in the present work provides acceptable analytical performance with relatively inexpensive equipment. In addition, the proposed CL method is rapid, simple, and less expensive than most of the reported methods (such as HPLC-UV in Table 2).

3.8. Interference study To assess the selectivity of proposed method, the experiments were performed by using a series of solutions containing 5.0 mg L-1 dexamethasone plus different amounts of interfering potentially interfering ions. The tolerance limit was defined as the amount of foreign substances that caused a relative error of less than ±5% in the CL signal for the determination of dexamethasone [18]. Thus, the effects of potentially interfering compounds were tested and the results are given in Table 3. As shown in Table 3, some cations interfere with the CL system. Thus, interference from these metal ions was removed by passing the real water sample solutions containing dexamethasone through a strong cation exchanger column. So, it is concluded that the CL method provides selective determination of dexamethasone in environmental water samples and pharmaceutical formulation.

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3.9. Analytical application study In order to prove the applicability and reliability of the developed method for real samples, it was applied to the determination of dexamethasone in water samples and commercial pharmaceutical formulation. The samples were prepared and analyzed according to the general process explained in the Section 2.5. The amounts of dexamethasone in the spiked water samples and commercial pharmaceutical formulation were obtained by a standard addition method, and the results are illustrated in Tables 4 and 5. Recovery tests were carried out to evaluate the accuracy of these methods. Also, the results of the analysis of these samples were compared with those obtained by the proposed CD-IMS method. It can be seen that there is no evident difference between the two developed methods based on the Student t-test (p=0.05). The obtained results confirm that the developed CL method affords good precision and accuracy for determination of dexamethasone in real samples.

4. Conclusions In this study, L-cysteine capped CdS QDs synthesized by using a facile hydrothermal method were successfully applied for the development of a sensitive and simple flow– injection CL method for the determination of dexamethasone. The CL reaction system of Lcysteine capped CdS QDs and KMnO4 could be remarkably enhanced in the presence of dexamethasone. The applicability of the flow–injection CL method was successfully proposed for the monitoring and determination of dexamethasone in spiked water samples and pharmaceutical preparations. Also, dexamethasone was determined using the CD-IMS method. Then, the analytical performance of the proposed flow–injection CL method was compared with those obtained by the CD-IMS method. A comparison of analytical results, such as LOD values, precision, and recoveries of these two analytical methods indicates that

17

the proposed CL system has higher sensitivity and precision than the CD-IMS method for the determination of dexamethasone.

Acknowledgments The authors thank the University of Tabriz (Iran) for the support provided. We also thank Aburaihan pharmaceutical Co. Tehran for providing the pharmaceutical.

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Figure captions Figure 1. Schematic diagram of flow-injection CL system; (a): acid solution; (b): sample or

standard solution of mixture of dexamethasone and L-cysteine capped CdS QDs; (c): H2O as the carrier; (d): KMnO4 solution; P: peristaltic pump; M: mixing tube; V: injection valve; F: flow cell; W: waste; D: detector (luminometer) and R: recorder (personal computer). Figure 2. (a): UV-Vis absorption spectra, and (b): PL spectra of L-cysteine capped CdS QDs

after different synthesis times at 150 °C. L-cysteine capped CdS QDs concentration: 1.0 mmol L-1 and excitation wavelength: 375 nm. Figure 3. (a): XRD pattern; (b): SEM; (c) particle size distribution and (d): FT-IR spectra of

the synthesized L-cysteine capped CdS QDs. Figure 4. Kinetic curves for (a): KMnO4–L-cysteine capped CdS QDs in acidic media, and

(b): KMnO4–L-cysteine capped CdS QDs CL system in the presence of dexamethasone in acidic media. The concentrations of KMnO4, H2SO4, L-cysteine capped CdS QDs, and dexamethasone were 0.08 mmol L–1, 1.0 mol L–1, 0.7 mmol L–1, and 8.0 mg L–1, respectively. Figure 5. Optimization of the CL reaction conditions: (a) effect of KMnO4 concentration.

Conditions: the concentrations of H2SO4, L-cysteine capped CdS QDs and dexamethasone were 0.5 mol L–1, 0.7 mol L-1, and 3.0 mg L-1, respectively; (b) effect of acidic media. Conditions: the concentrations of KMnO4 was 0.08 mmol L–1, other conditions were as in (b); (c) effect of size of L-cysteine capped CdS QDs. Conditions: H2SO4 concentration was 1.0 mol L–1, other conditions were as in (b); and (d): effect of L-cysteine capped CdS QDs concentration. Conditions: size of L-cysteine capped CdS QDs was 5.32 nm, other conditions were as in (c). Figure 6. CL spectra of (a): KMnO4–L-cysteine capped CdS QDs CL system in acidic media,

and (b): KMnO4–L-cysteine capped CdS QDs CL system in the presence of dexamethasone

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in acidic media. The concentrations of KMnO4, L-cysteine capped CdS QDs, dexamethasone, and H2SO4 were 0.08 mmol L–1, 0.7 mmol L–1, 5.0 mg L-1, and 1.0 mol L–1, respectively. Figure 7. UV–Vis absorption spectra of KMnO4–L-cysteine capped CdS QDs-

dexamethasone CL system, recorded at different time intervals after their mixing. Conditions: the concentrations of KMnO4, L-cysteine capped CdS QDs, H2SO4 and dexamethasone were 0.08 mmol L–1, 0.7 mmol L–1, 1.0 mol L–1 and 7.0 mg L–1, respectively. Figure 8. Ion mobility spectra of 5.0 mg L–1 dexamethasone and background.

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Figures

Figure 1

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Figure 4

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(d) Figure 5

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Figure 6

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Figure 7

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Figure 8

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Research highlights •

Synthesis and characterization of L-cysteine capped CdS quantum dots (QDs).

•

CL reaction of L-cysteine capped CdS QDs with KMnO4 as efficient oxidizing agent.

•

Dexamethasone determination using KMnO4–capped CdS QDs flow–injection CL system.

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