Development and validation of a rapid LC-MS/MS method to quantify letrozole in human plasma and its application to therapeutic drug monitoring

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• 作者：Rong Shao ; Ling-yan Yu ; Hong-gang Lou ; Zou-rong Ruan ; Bo Jiang and Jin-liang Chen
• 关键词：letrozole ; LC&ndash ; MS/MS ; therapeutic drug monitoring ; human plasma
• 刊名：Biomedical Chromatography
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：30
• 期：4
• 页码：632-637
• 全文大小：803K
• ISSN：1099-0801

文摘

A selective, rapid, and sensitive liquid chromatography–tandem mass spectrometry(LC-MS/MS) method was developed and validated for the determination of letrozole (LTZ) in human plasma, using anastrozole as internal standard (IS). Sample preparation was performed by one-step protein precipitation with methanol. The analyte and IS were chromatographed on a reversed-phase YMC-ODS-C₁₈ column (2.0 × 100 mm i.d., 3 µm) with a flow rate of 0.3 mL/min. The mobile phase consisted of water containing 0.1% formic acid (v/v) and methanol containing 0.1% formic acid (v/v). The mass spectrometer was operated in selected reaction monitoring mode through electrospray ionization ion mode using the transitions of m/z 286.2  217.1 for LTZ and m/z 294.1  225.1 for IS, respectively. The method was validated for selectivity, linearity, lower limit of quantitation, precision, accuracy, matrix effects and stability in accordance with the US Food and Drug Administration guidelines. Linear calibration curves were 1.0–60.0 ng/mL. Intra- and inter-batch precision (CV) for LTZ were <9.34%, and the accuracy ranged from 97.43 to 105.17%. This method was successfully used for the analysis of samples from patients treated with LTZ in the dose of 2.5 mg/day. It might be suitable for therapeutic drug monitoring of these patients and contribute to predict the risk of adverse reactions. Copyright