Simultaneous quantification of nicotine, cotinine, trans-3鈥?hydroxycotinine, norcotinine and mecamylamine in human urine by liquid chromatography-tandem mass spectrometry

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• 作者：Karl B. Scheidweiler ; Diaa M. Shakleya ; Marilyn A. Huestis ; ^{mhuestis@intra.nida.nih.gov}
• 关键词：Mecamylamine ; Nicotine ; Cotinine ; Trans-3&prime ; -hydroxycotinine ; Urine ; LCMSMS
• 刊名：Clinica Chimica Acta
• 出版年：2012
• 期刊代码：54_00098981
• 类别：med
• 出版时间：14 June, 2012
• 卷：413
• 期：11-12
• 页码：978-984
• 文件大小：264 K

摘要

Background

Mecamylamine is a nicotine antagonist under investigation in combination with nicotine replacement for smoking treatment.

Methods

A simple, rapid and reliable liquid chromatography tandem mass spectrometry (LCMSMS) method was developed and validated for quantifying nicotine, cotinine, trans-3鈥?hydroxycotinine, norcotinine and mecamylamine in human urine. Chromatography was performed on a Synergi PolarRP column with a gradient of 0.1%formic acid and 0.1%formic acid in acetonitrile at 0.25 ml/min with an 8-min total runtime. Analytes were monitored by positive mode electrospray ionization and multiple reaction monitoring mass spectrometry.

Results

Linear dynamic ranges were 1-500 ng/ml for nicotine and norcotinine, 0.5-500 ng/ml for trans-3鈥?hydroxycotinine, 0.2-500 ng/ml for cotinine, and 0.1-100 ng/ml for mecamylamine; correlation coefficients were consistently greater than 0.99, and all calibrator concentrations were within 20%of target. Extensive endogenous and exogenous interferences were evaluated. At 3 concentrations spanning the linear dynamic range of the assay, mean extraction efficiencies from urine were 55.1-109.1%with analytical recovery (bias) 82.0-118.7%and total imprecision of 0.7-9.1%. Analytes were stable for 24 h at room temperature, 72 h at 4 掳C, 72 h in autosampler at 15 掳C and after three freeze/thaw cycles.

Conclusion

This method is useful for monitoring mecamylamine, nicotine and nicotine metabolites in smoking cessation and other clinical nicotine research.