Environ. Sci. Technol. 2005, 39, 5824-5830
Micellar Catalyzed Degradation of Fenitrothion, an Organophosphorus Pesticide, in Solution and Soils† V I M A L K . B A L A K R I S H N A N , ‡,§ ERWIN BUNCEL,‡ AND G A R Y W . V A N L O O N * ,‡ Department of Chemistry, Queen’s University, Kingston, Ontario K7L 3N6, Canada, and National Water Research Institute, Environment Canada, 867 Lakeshore Road, Burlington, Ontario L7R 4A6, Canada
We report on a study of the decomposition of fenitrothion (an organophosphorus pesticide that is a persistent contaminant in soils and groundwater) as catalyzed by cetyltrimethylammonium (CTA+) micelles. The CTA micelles were associated with two types of counterions: (1) inert counterions (e.g. CTABr) and (2) reactive counterions (e.g. CTAOH). The reactive counterion surfactants used were hydroxide anion (HO-) as a normal nucleophile and hydroperoxide anion (HOO-) and the anion of pyruvaldehyde oxime (MINA-) as two R-nucleophiles. The reactivity order followed: CTABr < CTAOH < CTAMINA , CTAOOH. Treatment of the rate data using the Pseudo-Phase Ion Exchange (PPIE) model of micellar catalysis showed the ratio k2M/k2W to be less than unity for all the surfactants employed. Rather than arising from a “true catalysis”, we attributed the observed rate enhancements to a “concentration effect”, where both pesticide and nucleophile were incorporated into the small micellar phase volume. Furthermore, the CTAOOH/CTAOH pair gave an R-effect of 57, showing that the R-effect can play an important role in micellar systems. We further investigated the effectiveness of reactive counterion surfactants in decontaminating selected environmental solids that were spiked with 27 ppb fenitrothion. The solids were as follows: the clay mineral montmorillonite and SO-1 and SO-2 soils (obtained from the Canadian Certified Reference Materials Project). The reactive counterion surfactant solutions significantly enhanced the rate of fenitrothion degradation in the spiked solids over that obtained when the spiked solid was placed in contact with either 0.02 M KOH or water. The rate enhancements followed the order CTAOOH . CTAMINA ∼ CTAOH > KOH . water. We conclude that reactive counterion surfactants, especially with R-nucleophiles, hold great potential in terms of remediating soils contaminated by toxic organophosphorus esters.
Introduction In continuation of our structure-reactivity studies of organophosphorus (OP) esters with nucleophiles, metal ions, and * Corresponding author phone: (613)533-2633; fax: (613)533-6669; e-mail:
[email protected]. † Part 8 in a series titled “Mechanisms of abiotic degradation and soil-water interactions of pesticides and other hydrophobic organic compounds”. For part 7, see ref 11. ‡ Queen’s University. § National Water Research Institute, Environment Canada. 5824
9
ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 39, NO. 15, 2005
solvent effects (1-4), in the present paper we focus on the micellar catalyzed decomposition of OP pesticides. The organophosphorus pesticide, O,O-dimethyl-O-(3-methyl-4nitro)phosphorothioate (fenitrothion, 1), is a broad spectrum insecticide (5) used extensively throughout the world for the control of agricultural and forest pests. In Canada, its main application is for the control of the spruce budworm (6). The use of this toxic pesticide has resulted in contamination of both soils and groundwater, thus necessitating its safe removal from the environment. One major approach in the remediation of Hydrophobic Organic Compounds (HOCs) such as fenitrothion from soils involves the use of micelles in pump-and-treat remediation (7, 8). In this process, a surfactant solution is pumped into the soil through an inlet well near a contaminant plume. As the micelle solution flows through HOC-laden soil, the HOCs partition into the micelle and are transported toward an extraction well. Upon extraction, the contaminant can be decomposed off-site. In the case of fenitrothion, both Greenhalgh and coworkers (9) and Maguire and Hale (10) found that below pH 7 fenitrothion was subject to an SN2 attack on the methoxy carbon, while in alkaline systems, the products of reaction (3-methyl-4-nitrophenolate and the anion of dimethylphosphorothioic acid) were consistent with attack at phosphorus (9). At environmental pH (ca. 5-8), the typical half-life for the degradation of fenitrothion was found to be approximately 50 days (9), clearly showing that fenitrothion has the capacity for environmental persistence. More recently, we showed that fenitrothion degradation was catalyzed by alkali metal ethoxides in ethanol (4). The ethanolysis was shown to proceed via three different routes (Scheme 1): (1) attack at the phosphorus center; (2) attack at the aliphatic carbon of the methoxy group; and (3) attack at the C-1 position of the aromatic ring. However, at higher concentrations of catalyst, we reported a regioselectivity in attack at the phosphorus center. This regioselectivity in attack at P was also later observed in the catalyzed hydrolysis of fenitrothion in surfactant solutions (11), with attack at phosphorus increasing with surfactant concentration. Another approach that has been shown to be effective in degrading a variety of OP esters involves the use of reactive counterion surfactants. The counterions can be nucleophilic (e.g., cetyltrimethylammonium hydroxide, CTAOH) or even R-nucleophilic (e.g., CTAOOH). R-Effect nucleophiles are compounds which have a lone pair of electrons adjacent to the nucleophilic center and have an enhanced reactivity (1214) compared to a so-called “normal” nucleophile of either comparable structure (e.g., HO- vs HOO-) or comparable pKa or both. Bunton and Foroudian (15) showed that mixed CTA+ micellar systems containing both Cl- and HOO- as counterions were able to efficiently degrade p-nitrophenyl diphenyl phosphate. Meanwhile, Toullec and Moukawim demonstrated that CTA+ micellar systems containing only HOO- could easily be prepared and that CTAOOH promoted the rapid degradation of phosphorus compounds such as paraxon (a structural analogue of fenitrothion) (16). Oximates (such as pyruvaldehyde 1-oximate (CH3C(O)CHdNO-), MINA-) form another appealing class of R-nucleophile, since many have pKa’s in the environmentally interesting range of 7-10. For example, MINA has a pKa of 8.38. When paired with CTA+ micelles, CTAMINA has been demonstrated to be effective in accelerating the hydrolysis of a variety of phosphate esters (17) including paraxon. The model most commonly used to rationalize rate accelerations in the presence of micelles is the Pseudo-Phase 10.1021/es050234o CCC: $30.25
2005 American Chemical Society Published on Web 06/21/2005
SCHEME 1. Competitive Pathways Observed in the Degradation of Fenitrothion (11)
SCHEME 2: Representation of the Pseudo-Phase Ion Exchange (PPIE) Model of Micellar Catalysis
2-fold: (1) to evaluate the ability of various C16 cationic surfactants with inert, nucleophilic, or R-nucleophilic counterions to catalyze fenitrothion degradation and (2) to determine if the presence of environmental solids (the clay mineral montmorillonite and two well characterized soils chosen for their differing organic matter content) affected the decomposition of fenitrothion as mediated by these C16 surfactants.
Experimental Section
Ion Exchange (PPIE) model of micellar catalysis (Scheme 2) (18, 19). In Scheme 2, KS denotes the partition constant for substrate association with the micellar phase, and k2W and k2M denote the second-order rate constants for reaction with nucleophile (Nu) in the aqueous and micellar phases, respectively. The observed rate constant, kobs, is
kobs )
Nu k Nu 2W[Nu]W + k 2M[Nu]MKS(c - cmc)
1 + KS(c - cmc)
(1)
To isolate the portion of reaction occurring solely in the micellar phase
kobs ) -
k2W[Nu]W 1 + KS(c - cmc)
)
k2M[Nu]MKS(c - cmc) 1 + KS(c - cmc)
(2)
If the nucleophile is the only anion present, β describes its relative association with the micelle
[Nu]M )
β VM
(3)
where VM is the molar volume of the micelle (in L mol-1). Defining the left side of eq 2 as kcorr and substituting eq 3 into eq 2
kcorr )
( )
k2Mβ KS(c - cmc) VM 1 + KS(c - cmc)
(4)
Although Bunton suggests that the volume of the Stern layer (0.14 L mol-1) be used for VM (20), Toullec holds that since the substrate may penetrate beyond the Stern layer, VM should instead reflect the global volume of the micelle (21). Smallangle neutron scattering measurements have indicated that VM for a C16 micelle is 0.60 L mol-1 (22), and it is this value that will be used in this work. Given that cationic micelles can be used both to remove toxic phosphorus esters from soils and also to catalyze the degradation of the ester, our objective in this work was
Chemical Reagents. Fenitrothion. Fenitrothion (MM ) 277.25; 96.7%, gift from Sumitomo Chemicals) was purified as we described elsewhere (4). A fenitrothion stock solution was prepared by dissolving pure fenitrothion (20 µL) in dry dioxane (10 mL), yielding a final concentration of 9.54 × 10-3 M. In all kinetic studies, an aliquot of this stock solution (20 µL) was added to the quartz cuvettes, such that the total volume of the cuvette was 2.52 mL, yielding a fenitrothion concentration of 7.72 × 10-5 M in each kinetic run. Cetyltrimethylammonium Bromide (CTABr). Solutions of CTABr were prepared via serial dilution of a 0.0127 M CTABr stock solution prepared by dissolving CTABr (MM ) 364.5; 0.4618 g; 1.27 × 10-3 mol, Aldrich, 99%) in CO2-free water (100 mL). Cetyltrimethylammonium Hydroxide (CTAOH). CTAOH (10 wt %, Aldrich) was standardized against KHP, using phenolphthalein indicator. As CTAOH readily absorbs CO2 from air (17), care was taken to handle the compound under an inert Ar environment. Once the concentration of the stock solution was accurately known (0.345 M), stock solutions of various concentrations were prepared by serial dilution of the stock solution. By serial dilution of these stock solutions, solutions with the desired concentration of CTAOH were obtained. Hydrogen Peroxide (H2O2). Solutions of H2O2 were prepared via serial dilution of a 0.401 M stock solution prepared by mixing H2O2 (MM ) 34.02; 30 wt %, d ) 1.11 g mL-1; 4.1 mL; Aldrich) with CO2-free water (95.1 mL). Cetyltrimethylammonium Hydroperoxide (CTAOOH). Solutions of varying CTAOOH concentration were prepared directly in the cuvette by mixing the required volumes of 0.401 M H2O2, 0.0538 M CTAOH, and CO2-free water. Methyl Isonitrosoacetone (MINA) Solutions. Prior to preparing in solution, anti-pyruvic aldehyde 1-oxime, MINA (MM ) 87.09; Aldrich, 98%), was recrystallized from heptane. Then, a 0.0846 M stock solution was prepared by dissolving 0.1843 g of MINA (2.12 × 10-3 mol) in 25 mL of CO2-free water. CTAMINA. Solutions of CTAMINA were prepared by serial dilution of a 0.0206 M stock solution, which was prepared by mixing 25 mL of 0.0846 M MINA with 25 mL of 0.0468 M CTAOH (see above). VOL. 39, NO. 15, 2005 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
9
5825
Environmental Solids. Homoionic Montmorillonite. A 0.497 M solution of CaCl2 was first prepared by dissolving CaCl2 (MM ) 110.98; 27.584 g; 0.248 mol; Aldrich) in 500 mL of water. The CaCl2 solution was then added to 20 g of montmorillonite (Aldrich), resulting in the formation of a slurry. This slurry was transferred into dialysis tubing which was hung in a 6 L beaker of distilled, deionized water. To ensure that excess Ca2+ was washed off the montmorillonite, the water in the beaker was stirred and changed every 12 h over a period of 72 h. The montmorillonite was then dried overnight, in an oven set to 100 °C. SO-1 Soil. SO-1 soil (Canadian Certified Reference Materials Project, CCRMP) is a C-horizon of Rideau clay, a Regosolic soil, and contains 80% clay of mixed minerology. The major metal elements in this soil are as follows: Al (9.38%), Fe (6.00%), K (2.68%), Mg (2.31%), and Ca (1.80%). The carbon content of the soil was reported as being 0.25%. Prior to use, the soil was dried overnight, in an oven set to 100 °C. SO-2 Soil. SO-2 soil (CCRMP) is a B-horizon of a FerroHumic Podzol. The metals of note in this soil are as follows: Al (8.07%), Fe (5.56%), K (2.45%), Ca (1.96%), and Na (1.90%). The carbon content was reported as being 4.8 wt % (or an organic matter content of ca. 10%). Prior to use, the soil was dried overnight, in an oven set to 100 °C. Determining β Values for CTAOOH. For most of the surfactant systems used in this study, values of β (the degree of counterion association with the micelle) were readily available from the literature (21, 23). However, for CTAOOH, no such values were found. Consequently, the method of Nome and co-workers (23) was used to determine β for CTAOOH. Briefly, solutions of varying CTAOOH concentrations were prepared as described above. The specific conductance of each solution was determined, and a plot of conductance vs CTAOOH concentration was generated. This plot was fitted to a third-order polynomial function, whose first derivative yielded values for R () 1-β). Kinetic Studies. General. Kinetic runs by UV-visible spectrophotometry were followed using a Varian CARY3, thermostated to 25 °C. All reactions were carried out under pseudo-first-order conditions in which the concentration of base was at least 100 times greater than the initial substrate concentration, as described elsewhere (4). Remediation of Fenitrothion from Various Environmental Solids. Five hundred milligrams of environmental solid (montmorillonite, SO-1 soil, or SO-2 soil) was wetted with 100 µL of distilled water, and a 200 µL aliquot of a 0.0191 M fenitrothion stock solution was added, bringing the concentration of fenitrothion associated with the solid to 27.5 ppb. This mixture was stirred for 15 min to ensure that the fenitrothion was thoroughly mixed with the solid. After having been stirred, the mixture was allowed to stand for 1 h, whereupon 25 mL of the required surfactant or KOH solution was added, with mixing, to create a slurry. As a control, separate experiments were performed in which 25 mL of H2O was added to the solid, creating a neutral slurry. These slurry solutions were mixed using an orbital shaker. At regular intervals, a 1 mL aliquot of slurry was removed and added to a centrifuge tube containing 1 mL of 0.0252 M HCl in order to quench the reaction. The tube was shaken and then centrifuged for 5 min (at 10 000 rpm) to settle the solid material. The supernatant liquid (2 mL) was transferred by pipet to a quartz UV cuvette. Immediately prior to analysis, 0.5 mL of 0.0658 M KOH was added to the cuvette (to convert all phenol to the more strongly absorbing phenoxide), and the UV-vis absorbance at 398 nm (λmax for 3-methyl-4nitrophenoxide) was measured. Pseudo-first-order rate constants were obtained from the slope of plots of log(Ainf - At) vs time for all surfactants except CTAOOH, in which fenitrothion degraded too rapidly for the 5826
9
ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 39, NO. 15, 2005
determination of a rate constant by the methodology described above. Accordingly, half-lives were simply estimated from the initial absorbance values, using the equation [A]t ) [A]0e-kt. In an attempt to assess the utility of the overall methodology, a subsequent degradation experiment was conducted in soil in which a larger concentration of fenitrothion (i.e., a heavily contaminated soil) was used. A 200 mg sample of SO-2 soil was accurately weighed and 100 µL of distilled water was added to the solid, after which a 20 µL aliquot of pure fenitrothion was added, bringing the concentration of fenitrothion associated with the solid to 13.2%. This mixture was stirred for 15 min, using a magnetic stir-bar, to ensure that the fenitrothion was thoroughly mixed with the solid. After stirring, the mixture was allowed to stand for 1 h. After 1 h, 10 mL of 0.02 M CTAOOH solution was added to the soil, and after 1 min, a 0.1 mL aliquot of slurry was removed and added to a centrifuge tube containing 1.9 mL of 0.0252 M HCl to quench the reaction. The centrifuge tube was shaken and then centrifuged for 5 min to settle the solid material. The UV-vis spectrum was acquired as described above. Because of the speed of the reaction, the half-life was estimated based on the absorbance value of this sample.
Results and Discussion Overview. The effect of varying the counterion associated with the hexadecyltrimethylammonium (CTA+) micelles on the degradation of fenitrothion was explored. The counterions employed fit into two broad categories. First, we studied fenitrothion hydrolysis in the presence of KOH and the inert counterion surfactant, CTABr. Second, we investigated the use of reactive counterion surfactants to hydrolyze fenitrothion. The reactive counterions we used were the “normal” nucleophile, hydroxide (HO-), and the alpha (R)-nucleophiles, HOO- (hydroperoxide anion) and H3C(CO)CHdNO(pyruvic aldehyde oximate, MINA-). The R-nucleophiles were chosen since they possess an exalted reactivity compared to that of normal nucleophiles (12-14), and we wished to examine whether it would be possible to couple the phenomenon of micellar catalysis with the R-effect. Application of the Pseudo-Phase Ion Exchange (PPIE) model of micellar catalysis often requires corrections to the observed rate constant. These corrections were performed for both categories of cationic surfactant (inert counterion and reactive counterion), and the source of the observed rate enhancements was determined. It should be noted that while some uncertainty arises from curve fitting treatments, the uncertainty in no way affects the qualitative conclusions that are presented herein. Finally, we consider the feasibility of using selected surfactants for the degradation of fenitrothion in various soil matrices. Solution Kinetics: Dissection according to the PPIE Model of Micellar Catalysis. Reaction in CTABr, an Inert Counterion Surfactant. Two main approaches can be followed when studying reactions with hydroxide anion in the presence of inert (non-nucleophilic) counterion surfactants. The first approach is to perform the experiment without maintaining a constant concentration of inert counterion, while the second approach calls for the maintenance of a constant concentration of the counterion (i.e., by using added salts). Tee and Fedortchenko (24) showed that the second approach minimized problems associated with a nonuniform exchange of hydroxide for bromide in the hydrolysis of p-nitrophenyl alkanoates in CTABr micelles and gave data that were more amenable to treatment by the PPIE model of micellar catalysis. Therefore, in this work, the total bromide ion concentration (where bromide originates from CTABr or added KBr) was held constant at 0.01 M. Recall that in eq 4, β describes the relative association of all counterions with the micelle.
kcorr )
( )
k2Mβ KS(c - cmc) VM 1 + KS(c - cmc)
(4)
In the case described here, there are two anions which serve as counterions. The first is the inert (i.e., non-nucleophilic) bromide ion and the second is the nucleophilic hydroxide anion (i.e., β ) θBr + θOH). Consequently, the term β in eq 4 must be replaced by θOH, the relative association of hydroxide anion with the micelle. θOH is the solution to the quadratic equation given in eq 5 (see the Supporting Information for derivation)
θOH )
-b + xb2 - 4ac 2a
(5)
where and [Br-]T and [OH-]T are the total concentrations of
a ) (c - cmc) - KOH/Br(c - cmc) b ) [Br-]T + KOH/Br[OH-]T c ) βKOH/Br[OH-]T
FIGURE 1. Corrected rate constants for the reaction of fenitrothion (7.72 × 10-5 M) with 0.02 M KOH, in the presence of CTABr, at 25 °C. [Br-] was maintained at 0.01 M using KBr. The fit shown is to eq 4, where β ) θOH. Values for θOH are provided in Table S1 (Supporting Information) and are calculated using KOH/Br ) 0.048 (25).
TABLE 1. Summary of the Kinetic Parameters Determined by Fitting to Eq 4 for the Hydrolysis of Fenitrothion in Cationic Surfactants at 25 °C surfactant
bromide and hydroxide anions (0.01 and 0.02 M, respectively); KOH/Br is the exchange constant for bromide and hydroxide anion at the Stern layer of C16 surfactants (0.048 (25)). The hydrolysis of fenitrothion in 0.02 M KOH in the presence of CTABr micelles ([Br-]TOT ) 0.01 M) gave a saturation-style plot of kcorr vs (CCTABr-cmc) (Figure 1) that was fitted to eq 4 using the nonlinear least squares regression analysis program GraphPad Prism. The resulting values for KS and k2M are summarized, along with cmc, k2W, and R2 values in Table 1. Details of the dissection of kobs into micellar and aqueous components are presented in Table S1 (Supporting Information). Reactions in Reactive Counterion Surfactants. In an effort to obtain greater rate enhancements than those observed in the presence of CTABr, fenitrothion degradation was studied in CTA+ surfactants associated with both normal and R-nucleophilic counterions. Onyido et al. (26) previously showed that fenitrothion hydrolysis was efficiently catalyzed by R-effect nucleophiles, including hydroperoxide ions and oximate ions such as 2,3-butane-dione mono-oximate. Accordingly, we hydrolyzed fenitrothion in CTAOH (Figure 2A) and in the R-nucleophilic counterion surfactants CTAOOH (Figure 2B) and CTAMINA (Figure 2C). As expected, the R-nucleophilic anions further enhanced the reactivity of the surfactant system, with CTAOOH reacting faster than CTAMINA. The saturation-style curves were fitted (using GraphPad Prism) to eq 4, and the resulting values for KS and k2M are summarized, along with cmc, k2W, and R2 values, in Table 1. Details of the dissection of kobs into micellar and aqueous components are presented in Tables S2-S4 (Supporting Information). From Figures 1 and 2, it becomes apparent that fenitrothion is more rapidly degraded by reactive counterion surfactants than by CTA+, Br-/HO- systems. This enhanced reactivity arises simply because, in reactive counterion micelles, the nucleophile need not compete for space on the Stern layer with the inert bromide ion. It should be noted that for CTAOH, hydroxide is the only anion in solution, and consequently, β represents the fractional association of hydroxide to the Stern layer (i.e., β ) θOH). Although no inert ions are present in solutions of CTAOOH and CTAMINA, these solutions both contain hydroxide anions in addition to having HOO- or MINApresent. For solutions containing MINA-, Kb ) 2.45 × 10-6, while for HOO-, Kb ) 3.70 × 10-3; hence in both cases, the
k2W (M-1 s-1) KS (M-1) k2M (M-1 s-1) 10-3
2.43 × CTAOHc 2.43 × 10-3 CTAOOHc 0.497 CTAMINAc 1.15 × 10-3
CTABra,b
277 254 181 1244
10-3
2.89 × 1.66 × 10-3 9.48 × 10-2 7.80 × 10-4
R2
k2M/k2W
0.985 0.998 0.987 0.989
1.19 0.683 0.191 0.679
a K b θ OH/Br ) 0.048 (25). OH values are listed in Table S1 (Supporting Information). c β values are listed in Tables S2-S4 (Supporting Information).
hydroxide ion concentration will not significantly contribute to the reaction rate and was thus neglected. Generally, rate enhancements observed in micellar systems (compared to nonmicellar systems) are attributable to one of two reasons. First, there could be a reduction in the free energy of activation of the rate determining step of the reaction, which would be considered “true catalysis”. Therefore, the ratio k2M/k2W would be significantly greater than 1. This feature was observed by Brinchi and co-workers (27) in their study of the E2 elimination of 1,2-dichloro-1,2-diphenylethane in the presence of CTAOH, which produced a k2M/ k2W ratio of ca. 27. However, the k2M/k2W ratios presented in Table 1 clearly indicate that the current work does not produce “true catalysis”. An alternative explanation then is that the reactant is strongly incorporated into the micelle and that the resulting smaller reaction volume effectively increases the substrate concentration, producing the observed rate enhancements (a so-called “concentration effect”). For example, in reactions of 2,4-dinitrofluorobenzene or p-nitrophenyl diphenyl phosphate with phenoxide ion in the presence of CTABr, the ratio k2M/k2W was 1.3 and 0.5, respectively (28). However, the observed rate enhancements (i.e, kobs(micellar)/kobs(aqueous)) were approximately 1000fold faster in the micellar systems than in nonmicellar systems. This rationale has been confirmed in numerous other studies such as the following: the reaction of pnitrophenyl diphenyl phosphate in the presence of metallomicelles (29), in the nucleophilic catalysis of various phosphate and carboxylate esters in metallomicelles (30), and in the reaction of CTAMINA with paraoxon (21). Therefore, based on the data given in Table 1, we conclude that the rate enhancements observed in the reaction of fenitrothion with cationic micelles also arise from the socalled “concentration effect” (31). Meanwhile, enhanced reactivity was expected with R-nucleophiles. An R-effect comparison is generally based on at VOL. 39, NO. 15, 2005 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
9
5827
TABLE 2. Half-Lives for the Degradation of Fenitrothion on Environmental Solids by 0.02 M KOH or Selected Reactive Counterion Cationic Surfactant Solutions (0.02 M), at 25 °Ca,b solid
t1/2 in KOH (min)
t1/2 in CTAOH (min)
none 257 ( 13.4 12.5 ( 0.43 montmoril594 ( 53.4 27 ( 5 lonite SO-1 320.5 ( 18.5 18.7 (2 SO-2 475 ( 25 17.2 ( 1.46
t1/2 in CTAMINA (min)
t1/2 in CTAOOH (s)
14.1 ( 0.35 11.4 ( 1.5 25.4 ( 3.3
