Penetration of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes.

We aimed to quantify the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation, were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10 min. Whole corneas and samples of aqueous humor were then harvested and frozen, and drug concentrations analyzed by liquid chromatography tandem mass spectrometry. The mean corneal concentration of moxifloxacin was twice as high as ofloxacin, and the latter was twice as high as ciprofloxacin. The mean concentration of moxifloxacin in the aqueous humor was four times higher than the other antibiotics, and the mean concentrations of ciprofloxacin and ofloxacin were statistically similar. The amount of drug that penetrated the anterior chamber after a 10-min immersion was far below the safe limit of endothelial toxicity of each preparation. Moxifloxacin demonstrated far superior penetration into the cornea and anterior chamber of cadaver eyes compared to ciprofloxacin and ofloxacin. One should not expect endothelial toxicity with the commercial eye drops of ciprofloxacin, ofloxacin, and moxifloxacin that reach the anterior chamber through the cornea.

Penetration of 0. 3% ciprofloxacin, 0. 3% ofloxacin, and 0. 5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes

We aimed to quantify the penetration of ciprofloxacin, ofloxacin, and moxifloxacin into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes, not eligible for corneal transplantation, were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin, 0.3% ofloxacin, or 0.5% moxifloxacin for 10 min. Whole corneas and samples of aqueous humor were then harvested and frozen, and drug concentrations analyzed by liquid chromatography tandem mass spectrometry. The mean corneal concentration of moxifloxacin was twice as high as ofloxacin, and the latter was twice as high as ciprofloxacin. The mean concentration of moxifloxacin in the aqueous humor was four times higher than the other antibiotics, and the mean concentrations of ciprofloxacin and ofloxacin were statistically similar. The amount of drug that penetrated the anterior chamber after a 10-min immersion was far below the safe limit of endothelial toxicity of each preparation. Moxifloxacin demonstrated far superior penetration into the cornea and anterior chamber of cadaver eyes compared to ciprofloxacin and ofloxacin. One should not expect endothelial toxicity with the commercial eye drops of ciprofloxacin, ofloxacin, and moxifloxacin that reach the anterior chamber through the cornea.

Quantification of chlorpheniramine maleate enantiomers by ultraviolet spectroscopy and chemometric methods.

Chlorpheniramine maleate (CLOR) enantiomers were quantified by ultraviolet spectroscopy and partial least squares regression. The CLOR enantiomers were prepared as inclusion complexes with beta-cyclodextrin and 1-butanol with mole fractions in the range from 50 to 100%. For the multivariate calibration the outliers were detected and excluded and variable selection was performed by interval partial least squares and a genetic algorithm. Figures of merit showed results for accuracy of 3.63 and 2.83% (S)-CLOR for root mean square errors of calibration and prediction, respectively. The ellipse confidence region included the point for the intercept and the slope of 1 and 0, respectively. Precision and analytical sensitivity were 0.57 and 0.50% (S)-CLOR, respectively. The sensitivity, selectivity, adjustment, and signal-to-noise ratio were also determined. The model was validated by a paired t test with the results obtained by high-performance liquid chromatography proposed by the European pharmacopoeia and circular dichroism spectroscopy. The results showed there was no significant difference between the methods at the 95% confidence level, indicating that the proposed method can be used as an alternative to standard procedures for chiral analysis.

Enantioselective distribution of albendazole metabolites in cerebrospinal fluid of patients with neurocysticercosis.

AIMS: Albendazole (ABZ) is effective in the treatment of neurocysticercosis. ABZ undergoes extensive metabolism to (+) and (-)-albendazole sulphoxide (ASOX), which are further metabolized to albendazole sulphone (ASON). We have investigated the distribution of (+)-ASOX (-)-ASOX, and ASON in cerebrospinal fluid (CSF) of patients with neurocysticercosis. METHODS: Twelve patients with a diagnosis of active brain parenchymal neurocysticercosis treated with albendazole for 8 days (15 mg kg(-1) day(-1)) were investigated. On day 8, serial blood samples were collected during the dose interval (0-12 h) and one CSF sample was taken from each patient by lumbar puncture at different time points up to 12 h after the last albendazole dose. Albendazole metabolites were determined in CSF and plasma samples by h.p.l.c. using a Chiralpak AD column and fluorescence detection. Population curves for CSF albendazole metabolite concentration vs time were constructed. RESULTS: The mean plasma/CSF ratios were 2.6 (95% CI: 1.9, 3.3) for (+)-ASOX and 2.7 (95% CI: 1.8, 3.7) for (-)-ASOX, with the two-tailed P value of 0.9873 being non-significant. These data indicate that the transport of ASOX through the blood-brain barrier is not enantioselective, but rather depends on passive diffusion. The present results suggest the accumulation of the (+)-ASOX metabolite in the CSF of patients with neurocysticercosis. The CSF AUC(+)/AUC(-) ratio was 3.4 for patients receiving albendazole every 12 h. The elimination half-life of both ASOX enantiomers in CSF was 2.5 h. ASOX was the predominant metabolite in the CSF compared with ASON; the CSF AUC(ASOX)/AUC(ASON) ratio was approximately 20 and the elimination half-life of ASON in CSF was 2.6 h. CONCLUSIONS: We have demonstrated accumulation of the (+)-ASOX metabolite in CSF, which was about three times greater than the (-) antipode. ASOX concentrations were approximately 20 times higher than those observed for the ASON metabolite.

Enantioselective analysis of albendazole sulfoxide in cerebrospinal fluid by capillary electrophoresis.

Albendazole (ABZ) is a benzimidazole anthelmintic drug used in the treatment of neurocysticercosis. After oral administration, ABZ is rapidly oxidized to albendazole sulfoxide (ABZSO), which has an asymmetric sulfur center, and later to albendazole sulfone (ABZSO2). ABZSO is the active metabolite responsible for the therapeutic effect of the drug. Previous studies have demonstrated pharmacokinetic differences between the two enantiomers, with the predominance of (+)-ABZSO in human biological fluids. This article describes for the first time the enantioselective analysis of ABZSO in cerebrospinal fluid (CSF) using capillary electrophoresis. The samples were prepared by liquid-liquid extraction using chloroform:isopropanol (8:2 v/v). The resolution of ABZSO enantiomers was obtained with a fused-silica capillary (60 cm x 75 microm ID) using 20 mmol/L Tris, pH 7.0, with 3.0% w/w sulfated beta-cyclodextrin as running buffer. The coefficient of variations and % relative error obtained for both within-day and between-days assays were lower than 15%. The method was linear over the concentration range of 100 to 2,500 ng/mL for each enantiomer, indicating that it is suitable for the analysis of ABZSO enantiomers in CSF from patients medicated with ABZ.

Enantioselective assay of nisoldipine in human plasma by chiral high-performance liquid chromatography combined with gas chromatographic-mass spectrometry: applications to pharmacokinetics.

Nisoldipine, a second-generation dihydropyridine calcium antagonist, is a racemate compound used in the treatment of hypertension and coronary heart disease. This study presents an enantioselective HPLC-GC-MS method for the analysis of nisoldipine in human plasma and establishes confidence limits for its application to pharmacokinetic studies. Plasma samples were basified and extracted with toluene. The enantiomers were resolved on a Chiralcel OD-H column using hexane-ethanol (97.5:2.5, v/v) and the (+)- and (-)-fractions were collected separately with the diode array detector switched off. For the quantification of the nisoldipine enantiomers a GC-MS with an Ultra 1 Hewlett-Packard column was used with the detector operated in the single-ion monitoring mode with electron-impact ionization (m/z 371.35 and 270.20 for nisoldipine and m/z 360.00 for the internal standard, nitrendipine). The method proved to be suitable for pharmacokinetic studies based on the low quantification limit (0.05 ng/ml for each enantiomer) and the broad linear range (0.05-50.0 ng/ml for each enantiomer). Low coefficients of variation (<15%) were demonstrated for both within-day and between-day assays. No interference from drugs associated with nisoldipine treatment was observed. The enantioselective pilot study on the kinetic disposition of nisoldipine administered in the racemic form to a hypertensive patient using a multiple dose regimen revealed the accumulation of the (+)-enantiomer with an AUC(0-24) (+)/(-) ratio of approximately 8. Both enantiomers were quantified in plasma at a time interval of 24 h. This HPLC-GC-MS method is reliable, selective and sensitive enough to be used in clinical pharmacokinetic studies on the enantioselective disposition of nisoldipine in humans.

Enantiomeric determination of praziquantel and its main metabolite trans-4-hydroxypraziquantel in human plasma by cyclodextrin-modified micellar electrokinetic chromatography.

A capillary electrophoresis method for the simultaneous quantitation of praziquantel and its main metabolite trans-4-hydroxypraziquantel enantiomers in human plasma was developed and validated using cyclodextrin-modified micellar electrokinetic chromatography. Sample clean-up involved a single-step liquid-liquid extraction of plasma with toluene after the addition of NaCl. The complete enantioselective analysis was obtained in less than 7 min using 2% w/v sulfated beta-cyclodextrin as chiral selector and 20 mmol/L sodium deoxycholate as surfactant, in 20 mmol/L sodium borate buffer, pH 10. A 50 microm x 42 cm uncoated fused-silica capillary was used for the analysis, performed at a voltage of 18 kV and at 20 degrees C. The calibration curves were linear over the 125-625 ng/mL concentration range. The mean recoveries for praziquantel and trans-4-hydroxypraziquantel were up to 96 and 71%, respectively, with good precision. All four enantiomers were quantified at two concentration levels (200 and 600 ng/mL) with precision and accuracy below 15%. The quantitation limit was 50 ng/mL for (-)-(R)- and (+)-(S)-praziquantel and 62.5 ng/mL for (-)-(R)- and (+)-(S)-trans-4-hydroxypraziquantel, using 1 mL of human plasma.

Stereoselective analysis of fluvastatin in human plasma for pharmacokinetic studies.

Fluvastatin, an inhibitor of cholesterol biosynthesis, is commercialized as a racemic mixture of the (+)-3R,5S and (-)-3S,5R stereoisomers, although inhibition of HMG-CoA reductase mainly resides in the (+)-(3R,5S)-fluvastatin isomer. The aim of the present study was to analyze fluvastatin isomers in human plasma with application to studies on kinetic disposition. Plasma samples of 1 ml were eluted into 3 ml LC-18 Supelclean (Supelco) columns equilibrated with methanol and water. The columns were washed with water and acetonitrile and then eluted with methanol containing 0.2% diethylamine. The (+)-3R,5S and (-)-3S,5R isomers were separated by HPLC on a Chiralcel OD-H chiral phase column and detected by fluorescence (lambda(ex) 305 nm; lambda(em) 390 nm). The quantification limit was 0.75 ng for each isomer/ml plasma and linearity was observed up to 625 ng/ml. The relative standard deviations obtained for intra- and inter-assay precision were lower than 10% and the recovery was higher than 80% for both enantiomers. Application of the method to a stereoselective study on the pharmacokinetics of fluvastatin administered as a single oral dose (Lescol, 20 mg) to a healthy volunteer revealed stereoselectivity, with the highest plasma concentrations being observed for the (-)-3S,5R isomer (Cmax 92.4 vs. 60.3 ng/ml, AUC(0-infinity) 133.3 vs. 97.4 ng h/ml, Cl/f 150.2 vs. 205.2 l h(-1) and Vd/f 4.4 vs. 6.0 l/kg).

Enantioselective analysis of disopyramide and mono-N-dealkyldisopyramide in plasma and urine by high-performance liquid chromatography on an amylose-derived chiral stationary phase.

An enantioselective high-performance liquid chromatography method was developed for the simultaneous determination of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) enantiomers in plasma and urine. The drugs were extracted from plasma samples by liquid-liquid extraction with dichloromethane after protein precipitation with trichloroacetic acid; the urine samples were processed by liquid-liquid extraction with dichloromethane. The enantiomers were resolved on a Chiralpak AD column using hexane-ethanol (91:9, v/v) plus 0.1% diethylamine as the mobile phase and monitored at 270 nm. Under these conditions the enantiomeric fractions of the drug and of its metabolite were analyzed within 20 min. The extraction procedure was efficient in removing endogenous interferents and low values for the relative standard deviations were demonstrated for both within-day and between-day assays. The method described in this paper allows the determination of DP and MND enantiomers at plasma levels as low as 12.5 ng/ml and can be used in clinical pharmacokinetic studies.

Enantioselective HPLC analysis of propafenone and of its main metabolites using polysaccharide and protein-based chiral stationary phases.

HPLC on chiral stationary phases has been used for the enantioselective assay of propafenone (PPF), 5-hydroxypropafenone (PPF-50H) and N-despropylpropafenone (PPF-NOR) enantiomers. The results obtained on Chiralpak AD column showed that it is useful for the resolution of PPF and of its main metabolites, although the peaks obtained for PPF-NOR were not symmetrical under the conditions investigated. This column and circular dichroism-based detection system were used to determine the absolute configuration of the eluates. Furthermore, the influence of the mobile phase composition on the resolution of PPF and of its main metabolites was investigated on cellulose derivatives (Chiralcel OD-H and Chiralcel OD-R) and protein (Chiral AGP and Ultron ES-OVM)-based chiral stationary phases. The enantiomers of PPF were resolved on all the columns, except for the Ultron ES-OVM. This column, the Chiralpak AD and the Chiralcel OD-H columns were suitable for the resolution of the PPF-50H enantiomers. The PPF-NOR enantiomers were resolved on the Chiralpak AD, Chiral AGP and Chiralcel OD-R columns.

Enantioselective analysis of metoprolol in plasma using high-performance liquid chromatographic direct and indirect separations: applications in pharmacokinetics.

Direct enantioselective separation on chiral stationary phases and indirect separation based on the formation of diastereomeric derivatives were developed and compared for the HPLC analysis of R(+) and S(-)-metoprolol in human plasma. Plasma samples prepared using solid-phase extraction columns or liquid-liquid extraction were directly analyzed on a Chiralpack AD or on a Chiralcel OD-H columns, respectively. S-(-)-menthyl choroformate was also used to yield diastereomeric derivatives resolved on a RP-8 column. The methods were employed to determine plasma concentrations of metoprolol enantiomers in a pharmacokinetic study of single dose administration of racemic metoprolol to a healthy Caucasian volunteer phenotyped as extensive metabolizer of debrisoquine. The correlation coefficients among enantioselective metoprolol plasma concentrations (5-223 ng/ml) obtained by the three methods were equal or higher than 0.99. The direct method that employed the chiral column Chiralpak AD may be considered the most sensitive, although the three methods demonstrated interchangeable use in the pharmacokinetic investigation.

Enantioselectivity of debrisoquine 4-hydroxylation in Brazilian Caucasian hypertensive patients phenotyped as extensive metabolizers.

Debrisoquine (D), an antihypertensive drug metabolized to 4-hydroxydebrisoquine (4-OHD) by CYP2D6, is commonly used as an in vivo probe of CYP2D6 activity and can be used to phenotype individuals as either extensive (EMs) or poor metabolizers (PMs) of such drugs as beta-adrenergic blockers, tricyclic antidepressants, and class 1C antiarrhythmics. This report describes reversed-phase HPLC systems by which D and 4-OHD or S-(+) and R-(-)-4-OHD in urine are more selectively quantified without the need for derivatization techniques. We also studied the urinary excretion of R-(-)- and S-(+)-4-hydroxydebrisoquine in EM hypertensive patients in order to determine weather 4-OHD formation exhibits enantioselectivity. Twelve patients with mild to severe essential hypertension were admitted to the study. They received a single tablet of Declinax containing 10 mg debrisoquine sulfate. All the urine excreted during the following 8 h was collected. The debrisoquine metabolic ratio (DMR) was calculated as % of dose excreted as D/% of dose excreted as 4-OHD and the debrisoquine recovery ratio (DRR) was calculated as % of dose excreted as 4-OHD/% of dose excreted as D+4-OHD. Debrisoquine and its metabolite were determined in urine by HPLC using a reversed-phase Select B LiChrospher column, a mobile phase of 0.25 N acetate buffer, pH 5-acetonitrile (9:1, v/v) and a fluorescence detector. The limit of quantitation was determined to be 25.0 ng/ml for D and 18.75 ng/ml for 4-OHD. Intra- and inter-day relative standard deviations (RSDs) were less than 10%. All hypertensive patients studied showed a DMR of less than 12.6 or a DRR higher than 0.12 and were classified as EMs. Direct enantioselective separation on chiral stationary phase involved resolution of S-(+)-4-OHD and R-(-)-4-OHD on a Chiralcel OD-R column with a mobile phase of 0.125 N sodium perchlorate, pH 5-acetonitrile-methanol (85:12:3, v/v/v). The quantitation limit of each enantiomer was 3.75 ng/ml of urine. Intra- and inter-day RSDs were less than 10% for each enantiomer. A high degree of enantioselectivity in the 4-hydroxylation of D favouring the S-(+) enantiomer was observed, resulting in R-(-)-4-OHD not detected in the urine of the EM hypertensive patients studied.

Determination of ametryn herbicide by bioassay and gas chromatography-mass spectrometry in analysis of residues in drinking water.

A simple, rapid and quantitative bioassay method was compared to a gas chromatography/mass spectrometry (GC/MS) procedure for the analysis of ametryn in surface and groundwater. This method was based on the activity of ametryn in inhibiting the growth of the primary root and shoot of germinating letuce, Lactuca sativa L. seed. The procedure was sensitive to 0.01 microgram/l and was applicable from this concentration up to 0.6 microgram/l. Initial surface sterilization of the seed, selection of pregerminated seed of certain root lengths and special equipment are not necessary. So, we concluded that the sensitivity of the bioassay method is compatible with the chromatographic method (GC-MS). However, the study of the correlation between methods suggests that the bioassay should be used only as a screening technique for the evaluation of ametryn residues in water.

Enantioselective kinetic disposition of albendazole sulfoxide in patients with neurocysticercosis.

The enantioselectivity of the kinetic disposition of albendazole sulfoxide (ASOX) was investigated in 18 patients with neurocysticercosis treated with a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h). Serial blood samples were collected on the eighth day of treatment during the last dose interval, with prorogation up to 12 h. Albendazole sulfone (ASON) and enantiomers of ASOX were analyzed in plasma samples by HPLC using a Chiralpak AD column and detection by fluorescence. The pharmacokinetic parameters showing statistically significant differences between the (+) ASOX and (-) ASOX enantiomers are presented as respective means (95% CI) as follows: maximum plasma concentration, Cmax = 301.6 (179.7-423.5) vs 54.9 (21.9-87.9) ng.ml-1; elimination half-life, t1/2 = 5.2 (4.1-6.3) vs 3.3 (2.8-3.8) h, area under the plasma concentration-time curve, AUCss0-8 = 1719.2 (978.6-2459.8) vs 261.4 (102.9-419.8) ng.h.ml-1 and apparent clearance, Cl/fm = 5.8 (3.8-7.8) vs 54.0 (35.2-72.7) l.h-1.kg-1. The mean value of 9.2 (7.6-10.9) for the AUC0-8(+)-ASOX/AUC0-8(-)-ASOX ratio demonstrated plasma accumulation of the (+) enantiomer. Sulfone formation capacity, expressed by the AUCss0-8 ratio ASON/ASOX + ASON, was 8.0 (7.0-8.9). The present data indicate enantioselectivity in the kinetic disposition of ASOX in patients with neurocysticercosis.

Simultaneous determination of propafenone and 5-hydroxypropafenone enantiomers in plasma by chromatography on an amylose derived chiral stationary phase.

An enantioselective liquid chromatography method was developed for the simultaneous determination of propafenone (PPF) and 5-hydroxypropafenone (PPF-5OH) enantiomers in plasma. After liquid liquid extraction with dichloromethane, the enantiomers were resolved on a Chiralpak AD column using hexane-ethanol (88:12, v/v) plus 0.1% diethylamine as the mobile phase and monitored at 315 nm. Under these conditions the enantiomeric fractions of the drug and of its metabolite were analysed within 20 min. The extraction procedure resulted in absolute recoveries of 62.9 and 61.3% for (R)- and (S)-PPF, respectively, and of 57.6 and 56.5% for (R)- and (S)-PPF-5OH, respectively. This procedure was efficient in removing endogenous interferents as well the interference of an other PPF metabolite, N-despropylpropafenone (PPF-NOR). The calibration curves were linear over the concentration range 25-1250 ng/ml. Low values of the coefficients of variation were demonstrated for both within-day and between day assays. The method described in this paper allows the determination of PPF and PPF-5OH enantiomers at plasma levels as low as 25 ng/ml and can be used in clinical pharmacokinetic studies.

Simultaneous determination of albendazole sulfoxide enantiomers and albendazole sulfone in plasma.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of albendazole sulfoxide (ABZSO) enantiomers and albendazole sulfone (ABZSO2) in human plasma. The resolution of ABZSO enantiomers and ABZSO2 was obtained on a Chiralpak AD column using hexane-isopropanol-ethanol (81:14.25:4.75, v/v/v) as the mobile phase. The drugs were detected by fluorescence (lambda(exc) = 280 nm, lambda(em) = 320 nm). The drugs were extracted from 500 microl plasma with ethyl acetate, and after solvent evaporation, the residues were dissolved in the mobile phase and chromatographed. The method was precise and accurate for the three compounds, as judged by the coefficients of variation and relative errors observed. Linear standard curves were obtained in the concentration range of 5-2500 ng/ml for ABZSO enantiomers and 1-500 ng/ml for ABZSO2. A typical plasma concentration-time profile is presented for one patient under treatment for neurocysticercosis.

Enantioselective analysis of propafenone in plasma using a polysaccharide-based chiral stationary phase under reversed-phase conditions.

We present a method for the enantioselective analysis of propafenone in human plasma for application in clinical pharmacokinetic studies. Propafenone enantiomers were resolved on a 10-microm Chiralcel OD-R column (250 x 4.6 mm I.D.) after solid-phase extraction using disposable solid-phase extraction tubes (RP-18). The mobile phase used for the resolution of propafenone enantiomers and the internal standard propranolol was 0.25 M sodium perchlorate (pH 4.0)-acetonitrile (60:40, v/v), at a flow-rate of 0.7 ml/min. The method showed a mean recovery of 99.9% for (S)-propafenone and 100.5% for (R)-propafenone, and the coefficients of variation obtained in the precision and accuracy study were below 10%. The proposed method presented quantitation limits of 25 ng/ml and was linear up to a concentration of 5000 ng/ml of each enantiomer.

Enantioselective analysis of praziquantel in plasma samples.

A direct enantioselective high-performance liquid chromatography method is described for the quantitative determination of praziquantel enantiomers in plasma samples. The method involves two-step extraction of plasma with toluene, evaporation of the solvent and chromatography on a Chiralcel OD-H column using hexane-ethanol (85:15, v/v) as the mobile phase and detection at 220 nm. The assay satisfies all of the criteria required for use in clinical pharmacokinetic studies.

Therapy for neurocysticercosis: pharmacokinetic interaction of albendazole sulfoxide with dexamethasone.

Albendazole is considered the drug of choice for neurocysticercosis. It is frequently used in combination with dexamethasone to prevent the acute inflammatory reaction due to cysticercal death. It has been reported that dexamethasone increases the plasma level of albendazole sulfoxide, the active metabolite of albendazole. The pharmacokinetic interaction of albendazole sulfoxide with dexamethasone, associated or not with cimetidine, was investigated in 24 patients with active intraparenchymal brain cysticercosis. Eight of these patients received albendazole alone, eight received it in combination with dexamethasone, and eight received it in combination with both dexamethasone and cimetidine. The pharmacokinetic parameters maximum plasma concentration, time to maximum plasma concentration, absorption half-life, and absorption rate constant did not differ between groups, suggesting that the formation of albendazole sulfoxide was not altered by the administration of dexamethasone, combined or not with cimetidine. There were significant differences, however, in the parameters plasma concentration-time curve, oral clearance, elimination half-life, and elimination rate constant, suggesting that dexamethasone, combined or not with cimetidine, decreases the rate of elimination of albendazole sulfoxide.

Enantioselective analysis of albendazole sulfoxide in plasma using the chiral stationary phase.

We present a method for the enantioselective analysis of albendazole sulfoxide (ABZSO) in plasma for application in clinical pharmacokinetic studies. ABZSO enantiomers were separated on a 5-micron Chiralcel OB-H column (4.6 x 150 mm) using hexane:ethanol (93:7, v/v) as the mobile phase and fluorescence detection. ABZSO was extracted with chloroform:isopropanol (8:2, v/v) from 500-microliter aliquots of acidified plasma, with full drug recovery. The proposed method presented quantitation limits of 20 ng/ml for (-)ABZSO and 50 ng/ml for (+)ABZSO and was linear up to a concentration of 5,000 ng/ml of each enantiomer.