Journal of Pharmaceutical and Biomedical Analysis 2014-10-01

Validated LC-MS/MS method for the simultaneous determination of chlorambucil and its prodrug in mouse plasma and brain, and application to pharmacokinetics.

XinYi Wang, Quan Zhang, Qing Lin, Yue Zhang, Zhi-Rong Zhang

Index: J. Pharm. Biomed. Anal. 99 , 74-8, (2014)

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Abstract

A simple, sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous determination of chlorambucil (CHL) and the prodrug of chlorambucil (CHLS) in mouse plasma and brain tissue. Detection was performed on a Diamonsil ODS chromatography column using gradient elution with a mobile phase of 0.2% aqueous formic acid and acetonitrile. Mass spectrometry was carried out in multiple reaction monitoring mode using a positive electrospray ionization interface. Good linearity was found for CHLS and CHL in plasma and brain tissue in different linear ranges (r>0.9996). Intra-day and inter-day precision was within 9.11% and accuracy was not more than 11.07%. The validated method was successfully applied to the pharmacokinetic study of CHLS and CHL in mice after intravenous administration. Copyright © 2014 Elsevier B.V. All rights reserved.