Enantioseparation and determination of dufulin enantiomers in cucumber and soil by chiral liquid chromatography–tandem mass spectrometry

A simple and rapid method for enantioselective determination of dufulin in cucumber and soil was developed by liquid chromatography with tandem mass spectrometry. The enantiomers were separated on a Superchiral S‐OD chiral cellulose tris(3,5‐dimethylphenylcarbamate) column at 20°C, with a mixture of acetonitrile and water (0.1% formic acid; 52:48, v/v) as mobile phase at a flow rate of 0.65 mL/min. The pretreatment conditions were optimized using an orthogonal test, and the optimized method showed good linearity and sensitivity. The limits of detection and limits of quantification of two dufulin enantiomers were 0.006 and 0.02 mg/kg, respectively. The average recoveries of S‐enantiomer and R‐enantiomer in cucumber and soil were 80.61–99.83% and 80.97–102.96%, respectively, with relative standard deviations of 1.30–9.72%. The method was successfully applied to determine dufulin in real cucumber and soil samples. The results demonstrate that the method could facilitate further research on the differences between individual dufulin enantiomers with respect to metabolites and environmental fate and finally help reveal the complex interactions that exist between dufulin, humans and the environment.     

Use of chiral derivatization for the determination of dichlorprop in tea samples by ultra performance LC with fluorescence detection

Dichlorprop is available for agricultural use as a chiral pesticide. In this study, the stereoselective determination of dichlorprop enantiomers in tea samples such as green, black, jasmine, and oolong was developed by ultra performance LC with fluorescence spectrometry after covalent chiral derivatization. The separation was achieved on an Acquity BEH C18 column with the mobile phase consisting of 0.1% formic acid in acetonitrile/water at a flow rate of 0.4 mL/min. In the covalent chiral derivatization using (S)‐(+)‐4‐(N,N‐dimethylaminosulfonyl)‐7‐(3‐aminopyrrolidin‐1‐yl)‐2,1,3‐benzoxadiazole, the peak resolution between the S and R‐dichlorprop enantiomers was 2.6. LODs and LOQs values were 10 and 50 ng/mL standard solution. The linearity of the calibration curves yielded the coefficients (r² > 0.99, ranging from 0.05 to 5 μg/mL) of determination of each of the dichlorprop enantiomers. SPE extraction was used for the sample preparation of dichlorprop in various tea samples. Recoveries were in the range of 82.4–97.6% with associated precision values (within‐day: 82.4–95.8%, n = 6, and between‐day: 83.7–97.6% for 3 days) for repeatability and reproducibility. Based on this result, our method has been proven to be highly efficient and suitable for the routine assay of dichlorprop enantiomers in various tea samples. We propose that the ultra performance LC assay after covalent chiral derivatization would be the renewed tools in the era of chiral stationary platform for chiral pesticide residues in foods.     

Simultaneous determination of penthiopyrad enantiomers and its metabolite in vegetables,fruits, and cereals using ultra-high performance liquid chromatography–tandem mass spectrometry

Penthiopyrad is a novel succinate dehydrogenase inhibitor that has one chiral center and exists a metabolite, 1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxamide in its residue definition. An efficient analytical method for the simultaneous determination of penthiopyrad enantiomers and its metabolite in eight matrices were developed using modified quick, easy, cheap, effective, rugged, safe method, coupled with chiral stationary phase and ultra-high performance liquid chromatography–tandem mass spectrometry. The absolute configuration of penthiopyrad enantiomers was confirmed by polarimetry and electronic circular dichroism. Eight polysaccharide-based chiral stationary phases were evaluated in terms of the enantioseparation of penthiopyrad and separation-related factors (the mobile phase, flow rate and the column temperature) were optimized. To obtain an optimal purification, different sorbent combinations were assessed. The linearities of this method were acceptable in the range of 0.005 to 1 mg/L with R² > 0.998, while the limits of detection and quantification were 0.0015 mg/kg and 0.01 mg/kg for two enantiomers and its metabolite. The average recoveries of R-(-)-penthiopyrad, S-(+)-penthiopyrad and the metabolite ranged from 75.4 to 109.1, 69.5 to 112.8, and 70.0 to 108.5%, respectively. The intra-day and inter-day relative standard deviations were less than 18.8%. The analytical method was accurate and convenient, which can support their further research on stereoselective degradation, residual monitoring and risk assessment.     

Dispersive solid‐phase extraction combined with dispersive liquid‐liquid microextraction for simultaneous determination of seven succinate dehydrogenase inhibitor fungicides in watermelon by ultra high performance liquid chromatography with tandem mass spectrometry

In this study, a simple and accurate sample preparation method based on dispersive solid‐phase extraction and dispersive liquid‐liquid microextraction has been developed for the determination of seven novel succinate dehydrogenase inhibitor fungicides (isopyrazam, fluopyram, pydiflumetofen, boscalid, penthiopyrad, fluxapyroxad, and thifluzamide) in watermelon. The watermelon samples were extracted with acetonitrile, cleaned up by dispersive solid‐phase extraction procedure using primary secondary amine, extracted and concentrated by the dispersive liquid‐liquid microextraction procedure with 1,1,2,2‐tetrachloroethane, and then analyzed by ultra high performance liquid chromatography with tandem mass spectrometry. The main experimental factors affecting the performance of dispersive solid‐phase extraction and dispersive liquid‐liquid microextraction procedure on extraction efficiency were investigated. The proposed method had a good linearity in the range of 0.1–100 µg/kg with correlation coefficients (r) of 0.9979–0.9999. The limit of quantification of seven fungicides was 0.1 µg/kg in the method. The fortified recoveries of seven succinate dehydrogenase inhibitor fungicides at three levels ranged from 72.0 to 111.6% with relative standard deviations of 3.4–14.1% (n = 5). The proposed method was successfully used for the rapid determination of seven succinate dehydrogenase inhibitor fungicides in watermelon.     

Enantioselective determination of ketamine in dog plasma by chiral liquid chromatography–tandem mass spectrometry

Ketamine is an N‐methyl‐d ‐aspartate receptor antagonist that is usually used clinically as a racemic mixture. Its two enantiomers exhibit different pharmacological activities. To determine whether the enantiomers have different pharmacokinetic profiles, a chiral liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of ketamine enantiomers in dog plasma. The enantiomers of ketamine were extracted from 50 μL of plasma by methyl tert‐butyl ether. Adequate chromatographic retention and baseline resolution of the enantiomers were achieved within a runtime of 5 min on a chiral column coated with polysaccharide derivatives, using a gradient mobile phase of acetonitrile and 10 mm ammonium bicarbonate aqueous solution. Ketamine enantiomers were detected by mass spectrometry with multiple reaction monitoring mode using the transitions of m/z 238.3 → 125.9 for the analytes and m/z 237.1 → 194.1 for carbamazepine (internal standard). The method was linear over the concentration range from 0.5 to 500 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was 0.5 ng/mL. The intra‐ and inter‐day precision was <7.3% and 8.5% for R‐ and S‐ketamine, respectively. The accuracy was 92.9–110.4% for R‐ketamine and 99.8–102.4% for S‐ketamine. The method was successfully applied to characterize the stereoselective pharmacokinetic profiles of ketamine in beagle dogs.     

Simultaneous stereoselective analysis of naftopidil and O‐desmethyl naftopidil enantiomers in rat feces using an online column‐switching high‐performance liquid chromatography method

A novel online column‐switching chiral high‐performance liquid chromatography method was developed and validated for the simultaneous determination of naftopidil (NAF) and its O‐desmethyl metabolites (DMN) enantiomers in rat feces. Direct and multiple injections of supernatant from rat feces homogenate were allowed through the column‐switching system. Analyte extraction was performed on the Capcell Pak mixed‐functional column by acetonitrile–phosphate buffer (pH 7.4; 10 mm ; 8:92, v/v) flowing at 1 mL/min. Separation of NAF and DMN enantiomers was achieved on the Chiralpak IA column by methanol–acetonitrile–acetate buffer (pH 5.3; 5 mm ; 45:33:22, v/v/v) flowing at 0.5 mL/min. The analytes were measured with a fluorescence detector at 290 nm (λ_ex) and 340 nm (λ_em). The validated method showed a good linearity [22.5–15,000 ng/mL for (+)‐/(?)‐NAF; 35–25,000 ng/mL for (+)‐/(?)‐DMN] and the lowest limits of quantification for NAF and DMN enantiomers were 22.5 and 35 ng/mL, respectively. Both intra‐ and inter‐day variations were <10%. The assay was successfully applied to the fecal excretion of NAF and DMN enantiomers in rat after single oral administration of (±)‐NAF. Nonstereoselective excretion of (+)‐ and (?)‐NAF was found in feces, while stereoselective excretion of (+)‐ and (?)‐DMN was observed with higher excretion levels of (+)‐DMN, indicating that there may exist stereoselective metabolism for NAF enantiomers. Copyright © 2014 John Wiley & Sons, Ltd.     

Separation and quantitation of oxprenolol in urine and pharmaceutical formulations by HPLC using a Chiralpak IC and UV detection

Abstract  

A stereoselective HPLC method has been developed for the simultaneous determination of oxprenolol enantiomers in urine and pharmaceutical products. Enantiomeric resolution of oxprenolol was achieved on cellulose tris(3,5-dichlorophenylcarbamate) immobilized onto a 5 μm spherical porous silica chiral stationary phase (CSP) known as Chiralpak IC with UV detection at 273 nm. The mobile phase consisted of n-hexane:isopropanol:triethylamine 70:30:0.1 (v/v/v) at a flow rate of 1.0 cm³/min. The method was validated for its linearity, accuracy, precision, and robustness. The calibration curves were linear over the range of 0.5–75 μg/cm³, with a detection limit of 0.1 μg/cm³ for each enantiomer. An average recovery of 99.0% and a mean relative standard deviation of 2.6% at 40.0 μg/cm³ for S-(−)- and R-(+)-enantiomers were obtained. The overall recoveries of oxprenolol enantiomers from pharmaceutical formulations were in the range 97.5–99.0%, with RSDs ranging from 0.6 to 0.8%. The mean extraction efficiency of oxprenolol from urine was in the range of 86.0–93.0% at 0.5–5 μg/cm³ for each enantiomer. The assay method proved to be suitable as a chiral quality control for oxprenolol formulations using HPLC and for therapeutic drug monitoring.     

Surfactant‐assisted electromembrane extraction combined with cyclodextrin‐modified capillary electrophoresis for the separation and quantification of Tranylcypromine enantiomers in biological samples

Surfactant‐assisted electromembrane extraction coupled with cyclodextrin‐modified capillary electrophoresis was developed for the separation and determination of Tranylcypromine enantiomers in biological samples. This combination would provide a new strategy for selective and sensitive determination of target analytes. The addition of surfactant in the donor solution improved the analyte transport into the lumen of hollow fiber that resulted in an enhancement in the analytes migration into acceptor solution. Optimization of the variables, affecting proposed method, was carried out and best results were achieved with a 175 V potential as driving force of the electromembrane extraction, 2‐nitrophenyloctylether as the supported liquid membrane, donor solution containing 0.2 mM Triton X‐100 with pH 3 and 0.1 M HCl for acceptor solution. Then, the extract was analyzed using cyclodextrin‐modified capillary electrophoresis method for separation of Tranylcypromine enantiomers. The best results were obtained with a phosphate running buffer (100 mM, pH 2.0) containing 7% w/v hydroxypropyl‐α‐cyclodextrin. Under the optimum conditions, a low limit of detection (3.03 ng/mL), good linearity (R² > 0.9953), and relative standard deviations below 4.0% (n = 5) were obtained. Finally, this procedure was applied to determine the concentration of Tranylcypromine enantiomers in urine samples with satisfactory results.     

Separation and determination of the enantiomers of lactic acid and 2‐hydroxyglutaric acid by chiral derivatization combined with gas chromatography and mass spectrometry

Lactic acid and 2‐hydroxyglutaric acid are chiral metabolites that have two distinct d‐ and l ‐enantiomers with distinct biochemical properties. Perturbations of a single enantiomeric form have been found to be closely related to certain diseases. Therefore, the ability to differentiate the d and l enantiomers is important for these disease studies. Herein, we describe a method for the separation and determination of lactic acid and 2‐hydroxyglutaric acid enantiomers by chiral derivatization (with l‐ menthol and acetyl chloride) combined with gas chromatography and mass spectrometry. The two pairs of above‐mentioned enantiomers exhibited linear calibration curves with a correlation coefficient (R²) exceeding 0.99. The measured data were accurate in the acceptable recovery range of 88.17–102.30% with inter‐ and intraday precisions (relative standard deviations) in the range of 4.23–17.26%. The limits of detection for d‐ lactic acid, l‐ lactic acid, d‐ 2‐hydroxyglutaric acid, and l‐ 2‐hydroxyglutaric acid were 0.13, 0.11, 1.12, and 1.16 μM, respectively. This method was successfully applied to analyze mouse plasma. The d‐ lactic acid levels in type 2 diabetes mellitus mouse plasma were observed to be significantly higher (P < 0.05, t‐test) than those of normal mice, suggesting that d‐ lactic acid may serve as an indicator for type 2 diabetes mellitus.     

Direct chiral resolution of cloquintocet-mexyl and its application to in vitro degradation combined with clodinafop-propargyl

A simple chiral high‐performance liquid chromatography (HPLC) method with ultraviolet (UV) detection was developed and validated for measuring Cloquintocet‐mexyl (ClM) enantiomers and clodinafop‐propargyl (CP) using cellulose tris‐(3,5‐dimethylphenylcarbamate) (CDMPC) as chiral stationary phase (CSP). The effects of mobile phase composition and column temperature on the ClM enantiomer separation were investigated. Good separation was achieved by using a mixture of n‐hexane and n‐propanol as mobile phase. Based on the chiral HPLC method, enantioselective quantitative determination analysis methods for this herbicide combined with CP in diluted plasma were developed and validated. The assay method was linear over a range of concentrations (0.5–100 µg/mL) in diluted plasma and the mean recovery was greater than 80% for both enantiomers and CP. The limits of quantification and detection for both ClM enantiomers and CP were 0.5 and 0.2 µg/mL, respectively. Intra‐ and interday relative standard deviations did not exceed 10% for three tested concentrations. The result suggested that the degradation of ClM enantiomers was stereoselective in rabbit plasma, and both rac‐ClM and CP degraded quickly in plasma, showing that the main existing forms with biological effect in animals are their metabolites. Copyright © 2011 John Wiley & Sons, Ltd.     

Enantioselective Partitioning of Racemic Ibuprofen in a Biphasic Recognition Chiral Extraction System

Enantioselective partitioning of ibuprofen enantiomers in a biphasic recognition chiral extraction system was studied. A combination of hydrophobic L‐isobutyl tartrate in organic phase and hydrophilic β‐cyclodextrin derivative in aqueous phase is necessary to establish a biphasic recognition chiral extraction system. The studies performed involve an enantioselective extraction in a biphasic system, where ibuprofen enantiomers form four complexes with the β‐cyclodextrin derivative in aqueous phase and the D(L)‐isobutyl tartrate in organic phase, respectively. In these biphasic resolutions, the types and the concentrations of the extractants, pH and temperature all exert a considerable influence on the biphasic recognition process. Good enantioselectivities for ibuprofen enantiomers were obtained at pH≦2.5 and a ratio of 2:1 of [L‐isobutyl tartrate] to [HP‐β‐CD]. Biphasic recognition chiral extraction is of strong chiral separation ability, and may be very helpful to optimize the extraction systems and realize the large‐scale production of enantiomers.     

Magnetic solid‐phase extraction of benzoylurea insecticides by Fe3O4 nanoparticles decorated with a hyper‐cross‐linked porous organic polymer

A magnetic polytriphenylamine porous organic polymer was prepared through simple self‐polycondensation of triphenylamine followed by coprecipitation with Fe²⁺ and Fe³⁺. It was applied as a magnetic adsorbent for the extraction of six benzoylurea insecticides from tomato, cucumber, and watermelon samples before their high‐performance liquid chromatography and mass spectral detection. Under the optimized experimental conditions, the established method gave a low limit of detection ranging from 0.05 to 0.1 ng/g and a good linear response ranging from 0.2 to 40 ng/g with coefficients of determination >0.99. The method recoveries for spiked analytes at the concentrations of 3 and 15 ng/g in real samples were in the range of 87.7–106.7% with the relative standard deviations <6.4%. The results indicated that it had a good adsorption capability toward the target analytes due to the π‐stacking and hydrogen bonding interactions. The polymer material showed great potential in the efficient extraction of organic compounds from real samples with complex matrixes.     

Enantioselective analysis of zopiclone and its metabolites in plasma by liquid chromatography/tandem mass spectrometry

A high-performance liquid chromatographic method with triple-quadrupole mass spectrometry detection (LC-MS-MS) was developed and validated for the first time for the simultaneous quantification of zopiclone and its metabolites in rat plasma samples. The analytes were isolated from rat plasma by liquid–liquid extraction and separated using a chiral stationary phase based on an amylose derivative, Chiralpak ADR-H column, and ethanol–methanol–acetonitrile (50:45:5, v/v/v) plus 0.025% diethylamine as the mobile phase, at a flow-rate of 1.0 mL min⁻¹. Moclobemide was used as the internal standard. The developed method was linear over the concentration range of 7.5–500 ng mL⁻¹. The mean absolute recoveries were 74.6 and 75.7; 61.6 and 56.9; 72.5, and 70.7 for zopiclone enantiomers, for N-desmethyl zopiclone enantiomers and for zopiclone-N-oxide enantiomers, respectively, and 75.9 for the internal standard. Precision and accuracy were within acceptable levels of confidence (<15%). The method application in a pilot study of zopiclone kinetic disposition in rats showed that the levels of (+)-(S)-zopiclone were always higher than those of (−)-R-zopiclone. Higher concentrations were also observed for (+)-(S)-N-desmethyl zopiclone and (+)-(S)-N-oxide zopiclone, confirming the stereoselective disposition of zopiclone.     

Enantioseparation of N‐acetyl‐glutamine enantiomers by LC–MS/MS and its application to a plasma protein binding study

A novel chiral method was developed and validated to determine N‐acetyl‐glutamine (NAG) enantiomers by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Enantioseparation was achieved on a Chiralpak QD‐AX column (150 × 4.6 mm i.d., 5 μm) using methanol–water (50 mm ammonium formate, pH 4.3; 70:30, v/v) at a flow rate of 500 μL/min. The detection was operated with an electrospray ionization source interface in positive mode. The ion transition for NAG enantiomers was m/z 189.0 → 130.0. The retention time of N‐acetyl‐l ‐glutamine and N‐acetyl‐d ‐glutamine were 15.2 and 17.0 min, respectively. Calibration curves were linear over the range of 0.02–20 μg/mL with r > 0.99. The deviation of accuracy and the coefficient of variation of within‐run and between‐run precision were within 10% for both enantiomers, except for the lower limit of quantification (20 ng/mL), where they deviated <15%. The recovery was >88% and no obvious matrix effect was observed. This method was successfully applied to investigate the plasma protein binding of NAG enantiomers in rats. The results showed that the plasma protein binding of NAG enantiomers was stereoselective. The assay method also exhibited good application prospects for the clinical monitoring of free drugs in plasma.     

A chiral LC‐MS/MS method for the enantioselective determination of R‐(+)‐ and S‐(–)‐pantoprazole in human plasma and its application to a pharmacokinetic study of S‐(–)‐pantoprazole sodium injection

Pantoprazole, a proton pump inhibitor, is clinically used for the treatment of peptic diseases. An enantioselective LC‐MS/MS method was developed and validated for the simultaneous determination of pantoprazole enantiomers in human plasma. Pantoprazole enantiomers and the internal standard were extracted from plasma using acetonitrile. Chiral separation was carried on a Chiralpak IE column using the mobile phase consisted of 10 mm ammonium acetate solution containing 0.1% acetic acid–acetonitrile (28 : 72, v /v). MS analysis was performed on an API 4000 mass spectrometer. Multiple reactions monitoring transitions of m /z 384.1→200.1 and 390.1→206.0 were used to quantify pantoprazole enantiomers and internal standard, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00–10,000 ng/mL, the intra‐ and inter‐day precisions were below 10.0%, and the accuracy was within the range of –5.6% to 0.6%. This method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of S ‐(–)‐pantoprazole sodium injections. No chiral inversion was observed during sample storage, preparation procedure and analysis. While R ‐(+)‐pantoprazole was detected in human plasma with a slightly high concentration, which implied that S ‐(–)‐pantoprazole may convert to R ‐(+)‐pantoprazole in some subjects.     

Validation of an enantioselective LC–MS/MS method to quantify enantiomers of (±)‐OTX015 in mice plasma: Lack of in vivo inversion of (−)‐OTX015 to its antipode

A highly sensitive, specific and enantioselective assay has been validated for the quantitation of OTX015 enantiomers [(+)‐OTX015 and (−)‐OTX015] in mice plasma on LC–MS/MS‐electrospray ionization as per regulatory guidelines. Protein precipitation was used to extract (±)‐OTX015 enantiomers and internal standard (IS) from mice plasma. The active [(−)‐OTX015] and inactive [(+)‐OTX015] enantiomers were resolved on a Chiralpak‐IA column using an isocratic mobile phase (0.2% ammonia/acetonitrile 20 : 80, v /v) at a flow rate of 1.2 mL/min. The total run time was 6.0 min. (+)‐OTX015, (−)‐OTX015 and IS eluted at 3.34, 4.08 and 4.77 min, respectively. The MS/MS ion transitions monitored were m/z 492 → 383 for OTX015 and m/z 457 → 401 for IS. The standard curves for OTX015 enantiomers were linear (r ² > 0.998) in the concentration range 1.03–1030 ng/mL. The inter‐ and intraday precisions were in the range 2.20–13.3 and 8.03–12.1% and 3.80–14.4 and 8.97–13.6% for (+)‐OTX015 and (−)‐OTX015, respectively. Both the enantiomers were found to be stable in a battery of stability studies. This novel method has been applied to the study of stereoselective oral pharmacokinetics of (−)‐OTX015 and unequivocally demonstrated that (−)‐OTX015 does not undergo chiral inversion to its antipode in vivo in mice.     

2,4,6‐Triarylphosphinines versus 2,4,6‐Triarylpyridines: An Investigation of the Differences in Reactivity between Structurally Related Aromatic Phosphorus and Nitrogen Heterocycles

The novel atropisomeric pyridine derivative rac‐ 10 has been synthesized and structurally characterized. In contrast to its phosphorus analogue 3 , axially chiral 10 has a considerably lower rotational barrier as estimated by DFT calculations. However, the presence of the two enantiomers could be confirmed by means of chiral analytical HPLC analysis and by protonation experiments with a chiral acid. Compound rac‐ 10 could be further dehydrogenated by treatment with DDQ to the benzo(h)quinoline derivative rac‐ 12 . This conversion failed for the phosphorus analogue rac‐ 3 . Interestingly, although 2,4,6‐triarylphosphinines undergo facile C? H activation with [Cp*IrCl₂]₂ in the presence of NaOAc, this reaction does not proceed with the corresponding pyridine derivatives. On the other hand, the latter ones can be selectively ortho‐metalated with Pd(OAc)₂, leading to acetate‐bridged dimeric species, which could be unambiguously confirmed by means of X‐ray crystal structure analysis. The treatment of phosphinines with Pd(OAc)₂ led instead to the formation of the unusual cofacial oxidative coupling products 16 and 17 , which consist of a phosphorus‐containing cage structure.     

Reversed‐phase liquid chromatographic determination of enantiomers of atenolol in rat plasma using derivatization with Marfey's reagent

An HPLC method was established for enantioseparation of (R,S)‐atenolol (ATE) and determination of enantiomers in rat plasma. Marfey's reagent (1‐fluoro‐2,4‐dinitrophenyl‐5‐L‐alanine amide, FDNP‐L‐Ala‐NH₂, MR) was used as chiral derivatizing reagent with detection of diastereomers at 340 nm. It was shown that the R‐isomer eluted before the S‐isomer. The method was validated for linearity, repeatability, limits of detection and limit of quantification (LOQ). Recovery of ATE at LOQ was 92.8% for (R)‐ATE and 92.6% for (S)‐ATE. Copyright © 2009 John Wiley & Sons, Ltd.     

Hydrophobic deep eutectic solvent as a green extractant for high‐performance liquid chromatographic determination of tetracyclines in water samples

A green extractant, hydrophobic deep eutectic solvent was first introduced for extraction of tetracycline, oxytetracycline, and chlortetracycline from environmental water samples prior to high‐performance liquid chromatography determination. Deep eutectic solvents consist of methyltrioctylammonium chloride and various medium‐chain alcohols/acids, and are easy in preparation, low cost and toxicity, desirably biodegradable, and biocompatible. The overall time required for sample preparation was 6 min and the volume of organic solvent used for extraction was only 400 µL. Under the optimized extraction condition, the present method yielded low limit of detection (0.5–2.0 ng/mL), acceptable precision (relative standard deviations < 9.7%), good linearity from 2.0 to 500 ng/mL (r² ≥ 0.9991). This optimized procedure was applied for determination of tetracyclines in different water samples with desirable spiked recovery ranged from 77.5 to 87.6%. There is, therefore, a great potential to further expand application of the method for investigation of other ultra‐trace analyte(s) in environmental matrixes.     

Enantioselective LC–ESI–MS/MS method for quantitation of (−)-lumefantrine and (+)-lumefantrine in mice plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)-LFN and (+)-LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid-phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA-3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive-ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra- and inter-day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)-LFN and (+)-LFN, respectively. Both (−)-LFN and (+)-LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac-LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.