Development and validation of a sensitive LC/MS-MS method for the determination of letrozole in nude mice plasma and its application to a pharmacokinetic study

doi:10.5246/jcps.2018.10.068

Abstract

Abstract:

A sensitive, rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of letrozole (LTZ) in nude mouse plasma in the current study, which was successfully applied to a pharmacokinetic study. Using anastrozole as internal standard (IS), plasma samples went through a one-step protein precipitation with acetonitrile before determination. The analyte and IS were analyzed on a reversed-phase ZORBAX-SB-C₁₈column (4.6 mm×250 mm, 5 μm) with an isocratic mobile phase consisting of acetonitrile and water containing 0.1% formic acid (v/v) at a flow rate of 1.0 mL/min. The analyte and IS were detected by a triple-quadrupole tandem mass spectrometer, and electrospray and multiple reaction monitoring (MRM) were employed to select LTZ at m/z 286.4/217.1 and IS at m/z 294.1/225.3 simultaneously in the positive ion mode. The calibration curve showed good linearity ranging from 0.8–2000.0 ng/mL (r>0.99). The intra-day and inter-day precisions of LTZ were 4.0%–8.4%, with an accuracy of 98.6%–104.9%. Using this method, we successfully characterized the pharmacokinetics (PK) of LTZ by a one-compartment model with first-order absorption in female BALB/c nude mice.

Key words: LC-MS/MS, Letrozole, Nude mice, Pharmacokinetics

CLC Number:

R943

Supporting:

Junsheng Xue, Qingyu Yao, Jian Li, Wenjun Chen, Hong Su, Xiuyun Tian, Chunyi Hao, Tianyan Zhou. Development and validation of a sensitive LC/MS-MS method for the determination of letrozole in nude mice plasma and its application to a pharmacokinetic study[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(10): 665-674.

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