Determination of mianserin in human plasma by high performance liquid chromatography–electrospray ionization mass spectrometry (HPLC–ESI/MS): Application to a bioequivalence study in Chi

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• 作者：Ping Xu ; Huan-De Li ; Ben-Mei Chen ; Ning Ma ; Miao Yan ; Yun-Gui Zhu
• 关键词：Mianserin ; Cinnarizine ; LC– ; ESI/MS ; Determination ; Bioequivalence
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2008
• 期刊代码：65_07317085
• 类别：ch
• 出版时间：5 August 2008
• 卷：47
• 期：4-5
• 页码：994-999
• 文件大小：501 K

摘要

This study aims to develop a standard protocol for the bioequivalence study of mianserin hydrochloride tablets—a tetracyclic antidepressant drug. For this purpose, a rapid, convenient and selective method using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC–ESI/MS) has been developed and validated to determine mianserin in human plasma. Mianserin and the internal standard (I.S.), cinnarizine were extracted from plasma by N-hexane:dimethylcarbinol (98:2, v/v) after alkalinized with sodium hydroxide. LC separation was performed on a Thermo Hypersil-Hypurity C₁₈ (5 μm, 150 mm × 2.1 mm) with the mobile phase consisting of 10 mM ammonium acetate (pH 3.4)–methanol–acetonitrile (35:50:15, v/v/v) at 0.22 ml/min. The retention time of mianserin and cinnarizine was 3.4 and 2.1 min, respectively. Quadrupole MS detection and quantitation was done by monitoring at m/z 265 [M+H]⁺ for mianserin and m/z 369 [M+H]⁺ for cinnarizine. The method was validated over the concentration ranges of 1.0–200.0 ng/ml for mianserin. The recovery was 81.3–84.1%, intra- and inter-day precision of the assay at three concentrations were 9.6–11.4%with accuracy of 97.5–101.2%and the lower limit of quantitation (LLOQ) detection was 1.0 ng/ml for mianserin. The stability of compounds was established in a battery of stability studies, i.e., short-term and long-term storage stability as well as freeze–thaw cycles. This method proved to be suitable for the bioequivalence study of mianserin hydrochloride tablets in healthy human male volunteers.