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Enantioselective LC-ESI-MS/MS method for quantitation of (-)-lumefantrine and (+)-lumefantrine in mice plasma and application to a pharmacokinetic study.
- Source :
-
Biomedical chromatography : BMC [Biomed Chromatogr] 2020 Sep; Vol. 34 (9), pp. e4879. Date of Electronic Publication: 2020 Jun 08. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2020 John Wiley & Sons, Ltd.)
Details
- Language :
- English
- ISSN :
- 1099-0801
- Volume :
- 34
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biomedical chromatography : BMC
- Publication Type :
- Academic Journal
- Accession number :
- 32386241
- Full Text :
- https://doi.org/10.1002/bmc.4879