Rapid quantification of vincristine in mouse plasma using ESI-LC-MS/MS: Application to pharmacokinetic studies.

Abstract

A simple, rapid, and sensitive LC-MS/MS method for determining concentrations of the anticancer alkaloid vincristine in micro volumes of mouse plasma was developed and validated in positive ion mode. Separation of vincristine and the internal standard [2H3]-vincristine was achieved on an Accucore aQ column with a gradient mobile phase delivered at a flow rate of 0.4 mL/min and a run time of 2.2 min. Calibration curves were linear (r2 > 0.99, n = 8) up to 250 ng/mL, with a lower limit of quantitation of 2.5 ng/mL. The matrix effect and extraction recovery for vincristine were ranging 108-110% and 88.4-107%, respectively. The intra-day and inter-day precision of quality controls tested at 3 different concentrations were always less than 15%, and accuracy ranged from 91.7 to 107%. The method was successfully applied to evaluate the pharmacokinetic profile of vincristine in wild-type and CYP3A-deficient mice in support of a project to provide mechanistic insight into drug-drug interactions and to identify sources of inter-individual pharmacokinetic variability associated with vincristine-induced peripheral neuropathy.

• Authors: Yan Jin, Yang Li, Muhammad Erfan Uddin, Alex Sparreboom, Shuiying Hu
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 1168 Pg. 122591 (Apr 01 2021) ISSN: 1873-376X [Electronic] Netherlands
• PMID: 33684722 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Chemical References

• Vincristine

Topics

• Animals
• Chromatography, High Pressure Liquid (methods)
• Limit of Detection
• Linear Models
• Male
• Mice
• Reproducibility of Results
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tandem Mass Spectrometry (methods)
• Vincristine (blood, chemistry, pharmacokinetics)