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标题：Validation of an LC-MS/MS Method for the Determination of Propofol, Midazolam, and Carbamazepine in Rat Plasma: Application to Monitor Their Concentrations Following Co-administration
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作者：Mohamed Abo El Hamd ; Mitsuhiro Wada ; Rie Ikeda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2015
卷号：38
期号：8
页码：1250-1253
DOI：10.1248/bpb.b15-00191
出版社：The Pharmaceutical Society of Japan
摘要：Propofol (PRO) is a hypnotic used to induce and maintain general anesthesia. A risk of drug–drug interactions exists in cases of clinical co-administration of PRO and midazolam (MDZ) or carbamazepine (CBZ). Therefore a sensitive and rapid assay is needed to monitor these drugs. In this study, a sensitive and selective liquid chromatography-tandem mass spectrometry technique was developed for simultaneous determination of PRO, MDZ, and CBZ in plasma. Simultaneous selected reaction monitoring in the positive and negative ionization modes was used for mass detection. Analytes were isolated from plasma samples by a simple, economic, and rapid solid-phase extraction method. Chromatographic separations were achieved using a Chromolith Performance RP-18e analytical column (100×4.6 mm i.d.) with a mixture of acetonitrile–ammonium acetate buffer (10 mM, pH 3.5) (90 : 10, v/v) as the mobile phase. The method was fully validated for PRO, MDZ, and CBZ over concentrations ranging at 1–100, 2–100, and 7–1000 ng/mL, respectively, with acceptable validation parameters. Furthermore, the method was applied to monitor PRO and MDZ or CBZ following co-administration in rats.