Simultaneous determination of dextromethorphan, dextrorphan and doxylamine in human plasma by HPLC coupled to electrospray ionization tandem mass spectrometry: Application to a pharmacokinetic study

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• 作者：J.L. Donato^a ; ^{donato@atcgen.com.br} ; F. Koizumi^b ; A.S. Pereira^c ; G.D. Mendes^b ; ^c ; G. De Nucci^b ; ^c ; ^d
• 关键词：Quantification ; Volunteer ; LC&ndash ; MS/MS
• 刊名：Journal of Chromatography B ; Analytical Technologies in the Biomedical and Life Sciences
• 出版年：2012
• 期刊代码：124_15700232
• 类别：ch
• 出版时间：15 June, 2012
• 卷：899
• 期：Complete
• 页码：46-56
• 文件大小：729 K

摘要

In the present study, a fast, sensitive and robust method to quantify dextromethorphan, dextrorphan and doxylamine in human plasma using deuterated internal standards (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction (LLE) using diethyl-ether/hexane (80/20, v/v). Extracted samples were analyzed by high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase (acetonitrile/water/formic acid (90/9/1, v/v/v) during 4.0 min at a flow-rate of 1.5 mL min^鈭? into a Phenomenex Gemini^庐 C18, 5 渭m analytical column (150 脳 4.6 mm i.d.). The calibration curve was linear over the range from 0.2 to 200 ng mL^鈭? for dextromethorphan and doxylamine and 0.05 to 10 ng mL^鈭? for dextrorphan. The intra-batch precision and accuracy (%CV) of the method ranged from 2.5 to 9.5%, and 88.9 to 105.1%, respectively. Method inter-batch precision (%CV) and accuracy ranged from 6.7 to 10.3%, and 92.2 to 107.1%, respectively. The run-time was for 4 min. The analytical procedure herein described was used to assess the pharmacokinetics of dextromethorphan, dextrorphan and doxylamine in healthy volunteers after a single oral dose of a formulation containing 30 mg of dextromethorphan hydrobromide and 12.5 mg of doxylamine succinate. The method has high sensitivity, specificity and allows high throughput analysis required for a pharmacokinetic study.