Enantioselective LC-ESI-MS/MS determination of dropropizine enantiomers in rat plasma and application to a pharmacokinetic study
| Autor: | Rajesh Chandran, Ramesh Mullangi, Umesh Todmal, Neeraj Kumar Saini, Suresh P. Sulochana, Narayanan Balaji, Bhavesh Babulal Gabani |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Clinical Biochemistry Ethyl acetate 030226 pharmacology & pharmacy 01 natural sciences Biochemistry Analytical Chemistry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Drug Stability Limit of Detection Tandem Mass Spectrometry Drug Discovery medicine Animals Derivatization Molecular Biology Levodropropizine Chromatography High Pressure Liquid Pharmacology Chromatography 010401 analytical chemistry Selected reaction monitoring Reproducibility of Results Stereoisomerism General Medicine 0104 chemical sciences Rats Dropropizine chemistry Propylene Glycols Linear Models Stereoselectivity Enantiomer medicine.drug |
| Zdroj: | Biomedical chromatography : BMC. 33(3) |
| ISSN: | 1099-0801 |
| Popis: | We developed and validated a simple, sensitive, selective and reliable LC-ESI-MS/MS method for direct quantitation of dropropizine enantiomers namely levodropropizine (LDP) and dextrodropropizine (DDP) in rat plasma without the need for derivatization as per regulatory guidelines. Dropropizine enantiomers and carbamazepine (internal standard) were extracted from 50 μL rat plasma using ethyl acetate. LDP and DDP resolved with good baseline separation (Rs = 4.45) on a Chiralpak IG-3 column. The mobile phase consisted of methanol with 0.05% diethylamine pumped at a flow rate of 0.5 mL/min. Detection and quantitation were done in multiple reaction monitoring mode following the transitions m/z 237 → 160 and 237 → 194 for dropropizine enantiomers and the internal standard, respectively, in the positive ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 3.23-2022 ng/mL for each enantiomer. The intra- and inter-day precisions were in the ranges of 3.38-13.6 and 5.11-13.8 for LDP and 4.19-11.8 and 8.89-10.1 for DDP. Both LDP and DDP were found to be stable under different stability conditions. The method was successfully used in a stereoselective pharmacokinetic study of dropropizine enantiomers in rats following oral administration of racemate dropropizine at 100 mg/kg. The pharmacokinetic results indicate that the disposition of dropropizine enantiomers is not stereoselective and chiral inversion does not occur in rats. |
| Databáze: | OpenAIRE |
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