Study on the determination and chiral inversion of R-salbutamol in human plasma and urine by liquid chromatography-tandem mass spectrometry

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Ting ZhouWen Tan

Abstract

The chiral inversion has been a concerned issue during the research and development of a chiral drug. In this study, a sensitive chiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of salbutamol enantiomers in human plasma and urine. The chiral inversion mechanism of R-salbutamol was fully investigated for the first time by studying the effects of physicochemical factors, including pH, temperature and time. A fitted model to predict the chiral inversion ratio of R-salbutamol was proposed using a Box-Behnken design. All the samples were separated on an Astec Chirobiotic T column and detected by a tandem mass spectrometer in multiple reaction monitoring mode. Lower limit of quantification of 0.100ng/mL was achieved under the optimized conditions. The method was fully validated and successfully applied to the clinical pharmacokinetic study of R-salbutamol in healthy volunteers. Chiral inversion of R-salbutamol to S-salbutamol has been detected in urine samples. The results indicated that pH and temperature were two dominant factors that caused the chiral inversion of R-salbutamol, which should be taken into consideration during the analysis of chiral drugs. The chiral inversion o...Continue Reading

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Citations

Jan 16, 2016·Drug Testing and Analysis·Mario ThevisWilhelm Schänzer
Apr 9, 2016·International Journal of Legal Medicine·Karen M D Holm, Kristian Linnet
May 21, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Andrea Re DepaoliniEnrico Davoli
Dec 19, 2018·Journal of Analytical Toxicology·Fernando X MoreiraPaula G de Pinho

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