Development of a sensitive and rapid method for quantitation of (S)-(−)- and (R)-(+)-metoprolol in human plasma by chiral LC–ESI–MS/MS
| Autor: | Daxesh P. Patel, Primal Sharma, Swati Guttikar, Pritesh Contractor, Pranav S. Shrivastav |
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| Rok vydání: | 2014 |
| Předmět: |
Analyte
Resolution (mass spectrometry) Chromatographic separation Pharmaceutical Science Pharmacy Mass spectrometry Analytical Chemistry chemistry.chemical_compound Drug Discovery Electrochemistry Solid phase extraction LC–ESI–MS/MS Spectroscopy Medicine(all) Chromatography Biochemistry Genetics and Molecular Biology(all) lcsh:RM1-950 Selected reaction monitoring Extraction (chemistry) S-(−)-metoprolol R-(+)-metoprolol lcsh:Therapeutics. Pharmacology chemistry Human plasma Original Article Enantiomer Chiral column Ammonium acetate |
| Zdroj: | Journal of Pharmaceutical Analysis, Vol 4, Iss 1, Pp 63-79 (2014) Journal of Pharmaceutical Analysis |
| ISSN: | 2095-1779 |
| DOI: | 10.1016/j.jpha.2013.02.008 |
| Popis: | A selective, sensitive and high throughput liquid chromatography-tandem mass spectrometry (LCâESIâMS/MS) method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose-2 (250mmÃ4.6mm, 5μm) column. Solid phase extraction of (S)-(â)- and (R)-(+)-metoprolol and rac-metoprolol-d6 as an internal standard (IS) was achieved on Lichrosep DVB HL cartridges employing 200μL human plasma. Both the analytes were chromatographically separated with a resolution factor of 2.24 using 15mM ammonium acetate in water, pH 5.0 and 0.1% (v/v) diethyl amine in acetonitrile (50:50, v/v) as the mobile phase within 7.0min. The precursorâproduct ion transitions for the enantiomers and IS were monitored in the multiple reaction monitoring and positive ionization mode. The method was validated over the concentration range of 0.500â500ng/mL for both the enantiomers. Matrix effect was assessed by post-column analyte infusion experiment and the mean extraction recovery was greater than 94.0% for both the enantiomers at all quality control levels. The stability of analytes was evaluated in plasma and whole blood under different storage conditions. The method was successfully applied to a clinical study in 14 healthy volunteers after oral administration of 200mg metoprolol tablet under fasting conditions. The assay reproducibility is shown by reanalysis of 68 incurred samples. The suitability of the developed method was assessed in comparison with different chromatographic methods developed for stereoselective analysis of metoprolol in biological matrices. Keywords: S-(â)-metoprolol, R-(+)-metoprolol, Chiral column, Chromatographic separation, LCâESIâMS/MS, Human plasma |
| Databáze: | OpenAIRE |
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