Ozonation of the pharmaceutical compound ranitidine: Reactivity and kinetic aspects

Chemosphere 76 (2009) 651–656

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Chemosphere journal homepage: www.elsevier.com/locate/chemosphere

Ozonation of the pharmaceutical compound ranitidine: Reactivity and kinetic aspects Javier Rivas *, Olga Gimeno, Angel Encinas, Fernando Beltrán Departamento de Ingeniería Química y Química Física, Facultad de Ciencias, Avenida de Elvas S/N, 06071 Badajoz, Spain

a r t i c l e

i n f o

Article history: Received 16 January 2009 Received in revised form 14 April 2009 Accepted 15 April 2009 Available online 9 May 2009 Keywords: Endocrine disruptor Water remediation Ozone Kinetics Mineralization

a b s t r a c t Ranitidine has been ozonated under different operating conditions of pH, applied ozone dose, initial ranitidine concentration and presence or absence of free radical inhibitors. Results of ranitidine evolution with time indicate a high reactivity of this compound with molecular ozone. Mineralization levels achieved in the order of 20–25% suggest that the (CH3)2–N–CH2– moiety bonded to the furan ring could be separated from the rest of the ranitidine structure and further mineralized. Only alkaline conditions (pH = 11) are capable of increasing TOC conversion up to values close to 70%. Determination of the direct ozonation rate constant for ranitidine by means of competitive kinetics reveals an unacceptable dependence of the aforementioned constant with the reference compound reactivity. It is hypothesised that only reference compounds with reactivity similar to the target species should be used. Ó 2009 Elsevier Ltd. All rights reserved.

1. Introduction A vast collection of pharmaceuticals – including antibiotics, anticonvulsants, analgesics, cardiovascular drugs, etc. – have been found in the drinking water supplies and/or wastewaters of many countries (Environmental News Network, 2008). Since some of these compounds are very resistant to biological oxidation processes and usually get away intact from conventional treatment plants, it is inferred that the presence of residual pharmaceuticals in the environment and in aquatic systems in particular, represent a serious environmental problem. Pharmaceuticals may inflict serious toxic and other effects to humans and other living organisms. Additionally, as stated previously, these substances are usually present at extremely low concentrations, thus involving more complicated and laborious analytical methods for their accurate determination. Ranitidine (N-(2-{[5-dimethylamino-methyl]-2-furanil}-methylthioethyl)N-ethyl-nitro-1,1-diaminoethane) was introduced to the market in 1981 and is now extensively used in the treatment of active duodenal ulcer, active and benign gastric ulcer, pathogenic gastrointestinal hypersecretory conditions (i.e. Zollinger– Ellison Syndrome) and symptomatic relief of gastroesophageal refluxes (Harvey et al., 1998). It is a histamine H2-receptor antagonist that has a furan ring structure. Ranitidine is metabolized in the liver to ranitidine N-oxide, desmethyl ranitidine and ranitidine S-oxide, and approximately 70% of a dose of the drug is excreted in urine as the unchanged drug. * Corresponding author. Tel./fax: +34 924 289385. E-mail address: [email protected] (J. Rivas). 0045-6535/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.chemosphere.2009.04.028

There is scarce literature about oxidation of this environmentally relevant pharmaceutical. The processes applied for elimination of ranitidine from water are electrochemical (heterogeneous catalytic reaction between a semiconductor and water under a superimposed electric field) (Carlesi et al., 2007) and photochemical (under sunlight and oxygen) (Latch et al., 2003) oxidation. These works report on the efficiency of the technologies to eliminate the parent compound but there is no data about the evolution of the mineralization level. Ozone is a water treatment technology with an increasing acceptation and applicability in drinking water facilities and wastewater treatment plants dealing with pharmaceuticals (Ternes et al., 2003; Vogna et al., 2004; Snyder et al., 2006; Gagnon et al., 2008; Klavarioti et al., 2009). Ozone is an oxidizing agent showing a high reactivity with a large number of organic compounds. Ozone either decomposes in water to form free hydroxyl radicals (more powerful oxidants agents than ozone itself) or reacts selectively with certain functional groups (direct ozone reactions). This work tries to assess the main features in the degradation of an aqueous solution of ranitidine hydrochloride by means of ozonation. The aim of the work is to report both the parent compound conversion and the mineralization level achieved. In addition, some kinetics aspects are also addressed.

2. Materials and methods Ozonation experiments were carried out in a 1-L borosilicate glass reactor. An ozone–oxygen mixture was continuously bubbled into the solution through a diffuser placed at the bottom of the reac-

J. Rivas et al. / Chemosphere 76 (2009) 651–656

Time, min 0

20

40

60

80

100

120 5

a

0.8

4

0.6

3

0.4

2

0.2

1

0

0

2

0

20

1

4 40

6 60

8 80

100

3

CR/CR

o

1

CO (ppm)

tor. Ozone was produced from pure oxygen by using a Sander Laboratory Ozone Generator. The gas flow rate was kept constant at 40 L h1. The dissolved ozone in solution was determined by the indigo method (Bader and Hoigné, 1981) based on the decoloration of 5,5,7-indigotrisulfonate. For that purpose, a Thermo Spectronic Helios a spectrophotometer was used. Additionally, ozone in the gas phase was monitored by means of an Anseros Ozomat ozone analyzer. The analysis was based on the absorbance at 254 nm. Homogeneous experiments were conducted in sealed bottles by mixing a predefined amount of an ozone saturated aqueous solution with an aqueous solution of ranitidine and a reference compound. The amount of ozone was kept sufficiently low so at the end of the process both ranitidine and the reference compound could be easily measured. With the exception of some specific runs, aqueous solutions of ranitidine were prepared with no buffer, so initial pH was governed by the pKas of the organic compound (8.2 and 2.7). To avoid the interference of the radical pathway on the ranitidine ozonation, some runs were carried out in the presence of t-butanol. Ranitidine hydrochloride, catechol, hydroquinone, phenol, resorcinol and fumaric acid were purchased from Sigma–Aldrich and used as received. Organic solvents were HPLC grade obtained from Panreac. The total organic carbon content of the samples was measured using a Shimazdu TOC-VCSH TOC analyzer. The pH of the solution was measured with a Crison 507 pH-meter. Ranitidine was determined by high-perfomance liquid chromatography (Agilent Technologies, series 1100) with a Waters Spherisorb SAX column and UV detector. The analysis was performed in isocratic mode. The mobile phase used was a mixture of acetonitrile and 20 mM aqueous potassium phosphate at a 20:80 volume ratio, acidified by the addition of phosphoric acid. The wavelength used in the UV detector was 313 nm.

0 10 120

b

0.8

C/Co

652

0.6 0.4

RANITIDINE

0.2 0

0

2

4

6

8

1

10

c

0.8

3.1. Effect of operating variables 3.1.1. Influence of inlet ozone concentration To assess the reactivity of ranitidine towards ozone, in a first experimental series different ozone doses were tested in the range 5–35 ppm. Fig. 1a shows the time evolution profiles of the parent compound and dissolved ozone in the system. As observed, ranitidine immediately reacts with ozone. Thus, just 10 ppm of inlet ozone (gas flowrate 40 L h1) are sufficient to completely eliminate approximately 33 ppm of ranitidine. By considering the ozone at the reactor outlet and dissolved in the aqueous matrix, an apparent stoichiometric coefficient can be estimated:

Z global ¼

Rt C O3 inlet Q g t  0 C O3 outlet Q g dt  C O3 V MW Ranitidine ðC Ro  C R ÞV MW Ozone

ð1Þ

C O3 inlet and C O3 inlet are the ozone concentrations at the gas reactor inlet and outlet in ppm, respectively, Qg is the gas flow rate, t denotes time, C O3 is the dissolved ozone concentration in the liquid phase in ppm, V is the reaction volume and CR stands for ranitidine concentration in ppm (the subscript ‘‘0” refers to initial conditions). Application of Eq. (1) reveals that the higher the ozone dose applied, the higher the apparent stoichiometric coefficient. In any case, it should be pointed out that Zglobal incessantly decreases from the beginning of the process to reach a plateau when ranitidine is almost depleted (conversion above 80%). Thus, when 5 ppm of ozone were applied, Zglobal sharply decreased from roughly 4 mol of ozone per mol of ranitidine removed to values in the proximity of 1.5. If 10 ppm of ozone are fed the range of values for Zglobal goes from 5 to 2.5.

CTOC/CTOC

o

3. Results and discussion

0.6 0.4 0.2 0

0

20

40

60

80

100

120

Time, min Fig. 1. Ozonation of ranitidine. (a) Influence of inlet ozone concentration. Experimental conditions: T = 20 °C; pHinitial = 5.0; pHfinal = 3.5; Qg = 40 L h1; V = 0.8 L; CRo = 33 ppm; C O3 inlet (ppm) = : s, 5; h, 10; D, 20; O 35. (solid symbols correspond to dissolved ozone concentration, C O3 ). (b) Influence of initial ranitidine concentration. Experimental conditions: T = 20 °C; pHinitial = 5.0; pHfinal = 3.5; Qg = 40 L h1; V = 0.8 L; C O3 inlet = 20 ppm; CRo = (ppm) = : O, 52; s, 33; h, 20; D, 10. (open and solid symbols correspond to ranitidine and TOC evolution, respectively). (c) Influence of initial pH on mineralization. Experimental conditions: T = 20 °C; Qg = 40 L h1; V = 0.8 L; C O3 inlet = 20 ppm; CRo = 33 ppm; pHinitial and pHfinal: s, 5 and 3.5; h, 8 and 4.6; D, 10 and 4.4; O, 11 and 10.7.

From previous results it is suggested that a higher ozone dose is capable of removing/oxidising more intermediates leading to higher oxidant consumption. However this hypothesis is not completely validated by TOC evolution. Hence, a slight improvement in mineralization level achieved is experienced when increasing the ozone dose from 5–10 ppm (TOC conversion 13–14%) to 20 ppm (TOC conversion 24%) while no enhancement is observed when using 35 ppm of ozone (TOC conversion 22%). In any case, given the errors associated to TOC analysis, differences are not statistically significant and

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it seems that ozone concentration does not influence the mineralization degree. 3.1.2. Influence of ranitidine initial concentration Different concentrations of ranitidine were ozonated by keeping constant the rest of operating variables. Once more it was observed that the pharmaceutical compound could be removed in a few minutes regardless of the initial load (see Fig. 1b). Since the process is too fast, the uncertainty in the analytical results does not allow deducing conclusive statements, however, some simple calculations made at the initial stages of the process suggest that ranitidine removal rate at time zero does not depend on its initial concentration, i.e. the process shows an apparent zero order regarding ranitidine concentration. The previous results could indicate that the process is at least partially controlled by mass transfer. Similarly to the preceding experimental series, TOC evolution is not affected by the operating conditions and a constant conversion in the proximity of 20% is achieved after 120 min of reaction. In accordance to other oxidation processes, ozone is supposed to preferably react with the heterocyclic ring in the ranitidine structure (see embedded structure of ranitidine in Fig. 1b). Accordingly, it is probable that in a first stage the (CH3)2–N–CH2– moiety bonded to the furan ring could be separated from the rest of the ranitidine structure and further mineralized. If this hypothesis is considered, three of thirteen carbon atoms would be converted into CO2 so the TOC conversion should be approximately 23%, in agreement with the data obtained previously. Nitrate concentration measured at the end of some of the runs conducted also corroborated the previous hypothesis, i.e. approximately a 20–25% of the potential NO 3 that could be generated could be detected after 120 min of reaction. 3.1.3. pH influence A final experimental series was conducted by changing the initial reaction pH. Buffers were not employed in these experiments so the final pH after the treatment significantly dropped in some of the runs. Normally, when organic compounds show a high reactivity towards ozone, pH has a marginal effect on the observed removal rate. Thus, even in the case that the protonated/non dissociated form has commonly a lower direct rate constant with ozone than the dissociated form, both constant are high enough to impede the observation of any significant difference. This rule of thumb was applicable in the case of ranitidine ozonation. However, results obtained in TOC conversion were drastically different. Thus, Fig. 1c illustrates the TOC evolution in experiments conducted at initial pH in the range 5–11. As observed, increasing the initial pH value results in a higher mineralization level (up to 70% when the initial pH was set at 11). Nevertheless, the real pH effect can not be deduced from Fig. 1c. Hence, final pH values (due to acidic intermediate formation) after 120 min of treatment were 3.5, 4.6, 4.4 and 10.7 corresponding to runs initiated at pH 5, 8, 10 and 11, respectively. It has to be highlighted that the minimum pH change was achieved when the most alkaline conditions were used, coinciding with the best conditions in terms of TOC removal. It is clear that intermediates generated in the direct ozonation of ranitidine show a high recalcitrance towards the attack of molecular ozone. However, at high pH, the generation of free hydroxyl radicals is extensively enhanced because of the ozone decomposition catalyzed by OH (Beltrán, 2004). Hydroxyl radicals unselectively attack most of the byproducts to finally yield carbon dioxide and water (also nitrates and sulphates are commonly formed when these heteroatoms are present). 3.2. The direct rate constant ozone–ranitidine As stated previously, results obtained in the preceding experiments indicate that ozonation of ranitidine develops through di-

rect reaction with molecular O3. Nevertheless, in order to corroborate the previous hypothesis, some heterogeneous experiments were also conducted in the presence of tert-butanol (tBuOH), a well known free radical scavenger, at different pHs. Two main effects were noticed from these experiments (not shown). On one hand, similarly to runs conducted in the absence of tert-butanol, in the presence of the scavenger the pH had no effect on ranitidine removal rate, regardless of the tert-butanol concentration used (interval between 0.01 and 0.1 M). On another hand, the addition of t-BuOH involves a slight acceleration of the ranitidine conversion rate if compared to runs carried out under similar operating conditions in the absence of the scavenger. These results are not anomalous and have been reported previously (Carbajo et al., 2006). Two main reasons can be postulated to account for this particular effect: 1 – t-BuOH effectively scavenges any generated radical avoiding the molecular ozone decomposition through reaction with these free radicals. The consequence is a higher amount of molecular O3 available to react with ranitidine. 2 – Some substances (including t-BuOH) are capable of modifying (increase) the fluid-dynamic properties of gas–liquid systems (Lo´pez-Lo´pez et al., 2007), i.e. they can increase the volumetric mass transfer coefficient and, consequently, increase the ranitidine removal rate, which, as stated previously, is partially controlled by the transfer of O3 to the aqueous solution. 3.2.1. Homogeneous experiments The aforementioned effects would corroborate the direct ozonation as the only route of ranitidine elimination by ozone. The direct rate constant of the ranitidine–O3 reaction was firstly determined by carrying out a series of homogeneous runs completed at pH 2 and by using the competitive method. If this method is considered, a reference compound is simultaneously oxidised to the target compound so the following equations apply (in the absence of free radicals):

 dCdtR ¼ zR kR C R C O3 

dC Ref dt

)

¼ zRef kRef C Ref C O3

ð2Þ

where z is the stoichiometric coefficient (defined as mol of substrate removed per mol of ozone consumed), the subscript ‘‘Ref” stands for the reference compound and ki denotes the second order rate constant. Dividing and integrating:

C Ref dC R zR kR C R CR zR k R ¼ ; ln ¼ ln dC Ref zRef kRef C Ref C Ro zRef kRef C Refo

ð3Þ

The term kR can be easily calculated provided that the rate constant of the reference compound, kRef, is known. Three different reference compounds were tested, for instance phenol, resorcinol (1,3 benzenediol) and hydroquinone (1,4 benzenediol). Fig. 2 shows a plot of the right term in Eq. (3) versus the neperian logarithm of the normalized concentration for the three reference substances used. Slopes of the different plots are 23.3 (R2 = 0.97), 3.5 (R2 = 0.89) and 0.68 (R2 = 0.95) for phenol, resorcinol and hydroquinone as reference compounds, respectively. Considering that the reference compound rate constants are 1.3  103, 9.8  104 and 1.5  106 M1 s1 for phenol, resorcinol and hydroquinone (Neta et al., 1988), the following values of the term kR could be calculated (zR was assumed unity): 3.0  104 M1 s1, 3.4  105 and 1.0  106 M1 s1. As inferred from the previous estimations, kR significantly depends on the kinetic parameters of the reference compounds. Two main hypothesis are suggested, on one hand, it is possible that rate constants of reference compounds taken from literature are not correct or/and, on another hand, the competitive method used is not applicable/valid. From the ratios experimentally obtained before, the following expressions can also be obtained:

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-0.6 0 -0.5 -1 -1.5 -2 -2.5 -3 -3.5

-0.5

-0.4

-0.3

o

-0.2

-0.1

0

o

ln(CR/CR )

ln(CRef /C Ref )

ln(CRef /CRef) o

0

0

1

2

3

4

o

-4

-1.5

-6

-2

-2

-1.5

-1

-0.5

0

o

-1

ln(CR /CR )

-2

-0.5

ln(CR /CR )

0

-8

lated by the competitive method by only utilising one reference compound, errors associated to competitive methods suggest using more than one reference compound. These rate constants are thereafter used as reference compounds themselves and, as a consequence, the errors are propagated in time. Additionally, when using the competitive method, target and reference compounds are supposed to be removed by only two routes, i.e. the direct ozonation and through free HO radicals (HO radicals are assumed to be suppressed by the use of low pH), however other routes should also be considered leading to erroneous results. The presence of radicals (likely HO) at low pH has previously been suggested. Thus, Rivas et al. (2005) hypothesised the existence of active radicals at pH 1 when ozonating p-chlorobenzoic acid. The source and nature of these radicals might vary depending on the substrate. Free hydroxyl radicals can be formed by ozonation of hydroperoxides (Bailey, 1982) formed in the first stages of the ozonation:

R0 H þ O3 ! ROOH þ ðother intermediatesÞ

ð10Þ

ROOH þ O3 ! ROO þ HO þ O2

ð11Þ

Alternatively, the presence of organic radicals in ozonation processes capable of promoting the radical chain can not be discarded.

ln(CRef /CRef ) o

Fig. 2. Competitive ozonation of ranitidine in the presence of different phenolic compounds. Up figure = homogeneous experiments. Experimental conditions: T = 20 °C; V = 25 mL; pHinitial = 2; reference compound: s, phenol; h, resorcinol; D, hydroquinone. Bottom figure = heterogeneous experiments. Experimental conditions: T = 20 °C; C O3 inlet = 5.0 ppm, V = 0.8 L; pHinitial = 2. Reference compound: s, catechol; h, resorcinol; D, hydroquinone (solid symbols correspond to experiments in the presence of 0.01 M t-butanol).

8  8 > > > : : ROO ROOH

Radicals of the type R or RO can be generated according to (Bailey, 1982):

R0 H þ O3 ! R0 þ HO þ O2 zResorcinol kResorcinol 23:3 ¼ ¼ 6:66 3:5 zPhenol kPhenol zHydroquinone kHydroquinone 3:5 ¼ ¼ 5:15 0:68 zResorcinol kResorcinol zHydroquinone kHydroquinone 23:3 ¼ ¼ 34:3 0:68 zPhenol kPhenol

0

ð5Þ ð6Þ

Eqs. (4)–(6) clearly disagree with literature values. A step beyond was considered by completing some competitive experiments between the reference compounds chosen in this study (Fig. 3). From the slopes obtained in Fig. 3 the following relationships were obtained:

zResorcinol kResorcinol ¼ 4:26ðR2 ¼ 0:98Þ zPhenol kPhenol zHydroquinone kHydroquinone ¼ 3:36ðR2 ¼ 0:96Þ zResorcinol kResorcinol zHydroquinone kHydroquinone ¼ 1:19ðR2 ¼ 0:99Þ zPhenol kPhenol

0



R þ O3 ! R O þ O2 ð4Þ

ð7Þ ð8Þ ð9Þ

Eqs. (7) and (8) acceptably corroborates the ratios calculated when ranitidine was present in the media (Eqs. (4) and (5)). Eq. (9), as expected, notoriously differs from the value given in Eq. (6). The reason is that hydroquinone is an intermediate of phenol ozonolyis. Accordingly, when hydroquinone and phenol are simultaneously ozonated, Eq. (2) is not applicable. Resorcinol is a minor intermediate in phenol ozonation and Eq. (7) can be considered appropriate. From the previous experimental facts it is hypothesised that rate constants given in the literature should be taken with caution. Thus, it is recommended that when using the competitive method, at least three or four reference compounds should be used. A high number of rate constants found in the literature have been calcu-

ð12Þ

ð13Þ ð14Þ

From the previous reaction schemes, target compounds in competitive kinetics can be removed not only by direct ozonation but also by HO (in the absence of specific radical scavengers) or organic radicals. 3.2.2. Heterogeneous experiments In an attempt to corroborate these previous results, the competitive series was repeated in heterogeneous runs at pH 2 in the presence and absence of t-butanol. Since phenol seems to have a significant lower rate constant than ranitidine, this compound was substituted by catechol, additionally, fumaric acid was also used in competitive experiments. It has to be highlighted that when highly reactive substances are considered, expressions like Eqs. (2) and (3) are only applicable when fast pseudo first order kinetics develop in the process, i.e. when Hatta number is higher than 3 and lower than Ei/2 (Gurol and Nekouinaini, 1984). Fig. 2 shows the experimental results found in the presence and absence of t-butanol. The following slopes were obtained after plotting Eq. (3): 2.71 (R2 = 0.99), 3.86 (R2 = 0.99) and 0.66 (R2 = 0.99) for runs conducted in the presence of catechol, resorcinol and hydroquinone and absence of tert-butanol, respectively. Alternatively, slopes of 2.85 (R2 = 0.98), 5.83 (R2 = 0.98) and 0.62 (R2 = 0.99) were obtained when tert-butanol was added to the reaction media. With the exception of resorcinol, the presence of the radical scavenger seems to exert no appreciable influence on the relative removal rate of ranitidine. Thus, by considering the reported kRef in the literature, the following kR values in the absence and presence of tert-butanol were calculated: 8.4 and 8.8  105 M1 s1 (reference = catechol), 3.8 and 5.7  105 M1 s1 (reference = resorcinol) and 9.9 and 9.3  105 M1 s1 (reference = hydroquinone), respectively. Again some features should be highlighted.

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ln CPhenol/CPhenol -0.13

-0.11

-0.25 -0.1

-0.2

o

o

-0.15

-0.1

-0.5 -0.1

0

0.1

0.2

0.3

0.4

0.5 0

0

-0.2

-0.2

-0.4

-0.4

-0.6

-0.6

-0.8

-0.8

-1

-0.5 -0.6 -0.25

-0.2

-0.15

-0.1

-0.4 -0.5 -0.6

0

-0.7

ln CResorcinol /CResorcinol 0

o

-0.4

ln CCatechol/CCatechol

-0.3

-0.3

ln CCatechol /CCatechol

o

-0.1 -0.2

-0.1

-0.05

ln CResorcinol/CResorcinol

o

0

-1.2

-1 -1.2 -0.3

0.1

0.2

o

0.3

0.4 0 -0.5

-0.2

-1

-0.4

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-0.6

-2

-0.8

-2.5

-0.2

-0.1

-3 0.1

0

ln CResorcinol/CResorcinol

o

0

0

0.1

0.2

0.3

0.4

0.5

0.6 0 -0.5

o

-0.6

ln CResorcinol /CResorcinol o

0

-0.2

ln CHydroquinone/CHydroquinone

-0.4

-0.5

-0.35

-0.3

ln CHydroquinone/CHydroquinone

ln CHydroquinone/CHydroquinone

-0.3

-0.3

-0.2

o

-0.25

-0.2

ln CHydroquinone/CHydroquinone

-0.2

o

ln CResorcinol/CResorcinol

-0.15

-0.4

o

o

-0.15 -0.1

ln CPhenol/CPhenol

ln CResorcinol/CResorcinol

o

-1

-1.2 -0.3 -0.25 -0.2 -0.15 -0.1 -0.05

-1 -1.5 -2 -2.5

0

-3

ln CCatechol/CCatechol

o

Fig. 3. Competitive ozonation of different phenolic compounds. Up figure = homogeneous experiments. Experimental conditions: T = 20 °C; V = 25 mL; pHinitial = 2. Bottom figure = heterogeneous experiments. Experimental conditions: T = 20 °C; C O3 inlet = 5.0 ppm, V = 0.8 L; pHinitial = 2 (Solid symbols correspond to experiments in the presence of 0.01 M t-butanol).

Thus, kR highly depends on kRef, apparently it is hypothesised that the closer kR and kRef are, the more accurate the value of kR seems to be. The relative removal ratios between reference compounds could be calculated by comparison of experiments in the presence of ranitidine:

zCatechol kCatechol ¼ 1:42 ðno t  BuOHÞ; 2:04 ðwith t  BuOHÞ ð15Þ zResorcinol kResorcinol zHydroquinone kHydroquinone ¼ 5:85 ðno t  BuOHÞ; 9:40 ðwith t  BuOHÞ zResorcinol kResorcinol ð16Þ zHydroquinone kHydroquinone ¼ 4:10 ðno t  BuOHÞ; 4:60 ðwith t  BuOHÞ zCatechol kCatechol ð17Þ Additionally the previous ratios were also obtained by direct determination in specific runs (Fig. 3). The results were 2.86 (no t-BuOH) and 3.81 (with t-BuOH) for Eq. (15), 4.66 (no t-BuOH) and 5.91 (with t-BuOH) for Eq. (16) and finally 3.84 (no t-BuOH) and 3.93 (with t-BuOH) for Eq. (17). Literature values are 3.16, 15.31 and 4.84 for Eqs. (15)–(17), respectively. From the precedent analysis it can be stated again that competitive methods are only accurate when ozone reaction rate constants of the studied compounds are similar.

The presence of tert-butanol shows two particular features. On one hand, t-BuOH consistently increases the ratio between rate constants in favour of the most reactive substance, although differences (with some exceptions) are not excessive. On another hand, t-BuOH always increases the removal rate of individual compounds. The hypothetical formation of HO (or any other t-BuOH scavenged radical) from the direct ozonolysis of parent compounds would explain both effects (i.e. a higher molecular ozone concentration is available when radicals are trapped by t-BuOH). Fumaric acid with a rate constant of 6.0  103 M1 s1 was ozonated in the presence of ranitidine (results not shown), no appreciable conversion of the acid was experienced (both in the absence and presence of t-BuOH). From an experimental point of view, these results are somehow unexpected. Thus, when phenol, with a lower rate constant of 1.3  103 M1 s1 was used, some phenol conversion was obtained. The previous results suggest that oxidation of ranitidine involves the formation of active species capable of attacking phenol. This synergistic effect should be considered when using competitive kinetics. An alternative method to calculate the value of the ranitidine– ozone reaction rate constant was also considered. When fast kinetics applies in second order irreversible heterogeneous ozonation processes, the following equation describes the kinetics (Beltra´n et al., 1995):

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"sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi # Ha2 HaEi Ha  ¼ kL aC O3 þ þ1 2ðEi  1Þ 4ðEi  1Þ2 Ei  1

ð18Þ

CO3 is

where N O3 is the ozone adsorption rate, the ozone concentration in the gas–water interface, kLa the volumetric mass transfer coefficient, Ha the Hatta number and Ei the instantaneous reaction factor. The previous parameters are defined as follows:

ð19Þ ð20Þ

DO3 and DR are the diffusivities of ozone and ranitidine, respectively, and kL the individual liquid phase mass transfer coefficient. At initial conditions it follows that:

NO3

 t¼0

  1 dC R ¼ z R dt t¼0

ð21Þ

Also, at time zero it is supposed that ozone is only consumed by the parent compound, so the theoretical outlet ozone should be:

C O3 outlet ¼

h   C O3 inlet  Q  1zR  dCdtR

t¼0

Q

The authors thank the economic support received from the CICYT of Spain and European FEDER Funds through Projects CTQ 2006/ 04745 and CSD2006-00044. Finally, Mr. Encinas acknowledges the Ministry of Science and Education of Spain through Grant FPI. References

pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi kR DO3 C R Ha ¼ k sffiffiffiffiffiffiffiffi"L # DO3 DR C R Ei ¼ 1þ DR zR DO3 C O3



Acknowledgements

V

i ð22Þ

Accordingly, C O3 is calculated by the corresponding Henry´s law.The following values were considered: zR = 1, kL = 4.6x105 m s1, kLa = 3.5  103 s1, DR = 4.4  1010 m2 s1, DO3 = 1.76  109 m2 s1 (Beltra´n et al., 1995; Wilke and Chang, 1955; Johnson and Davis, 1996). This method can only be applied to fast reactions, i.e. for those reactions complying with 10Ei > Ha > 1. Hence, only the experiment conducted with the lowest inlet ozone concentration could be used. The set of reactions 18–22 was solved by means of the EXCEL add-in SOLVER. The value of kR obtained was 1.56  105 M1 s1, additionally Hatta number was 3.4 while 10Ei was 30.7, confirming the fast regime developed. In any case, given the uncertainty in the determination of some parameters involved in the calculation procedure (i.e. DR is theoretically calculated, initial ranitidine removal rate can also be another error source, Henry’s constant is also based on literature values, etc.), this method should only be considered as a mere tool to evaluate in a rough way the kinetics of fast ozonation regimes.

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