摘要
建立一种快速测定人血浆中8'-羟基二氢麦角隐亭(8'-OH-DHEC)浓度的LC-MS/MS法,以曲马多为内标,采用C18反相柱(150 mm×2.0 mm,5μm),柱温35℃。流动相为甲醇-水(含0.1%甲酸),流速0.2 mL/min;电喷雾离子化(ESI),正离子扫描,选择性反应监测(SRM)8'-OH-DHEC m/z 594.3→270.0;曲马多m/z 264.1→58.3。本方法专属性强,8'-OH-DHEC在50～4 000 pg/mL呈良好的线性关系,r=0.999 3,最低检测浓度为50 pg/mL,低、中、高浓度下的日内及日间精密度、准确度、稳定性等均符合生物样品测定要求。本方法应用于22名健康受试者口服4 mg麦角隐亭的生物等效性研究,结果表明此方法专属性强,快速灵敏,适用于临床剂量下麦角隐亭药代动力学及生物等效性研究。
A sensitive,selective and simple liquid chromatography tandem mass spectrometry（LC-MS/MS） method was developed for determining the major active metabolite 8′-hydroxy-dihydroergocryptine（8′-OH-DHEC） of α-dihydroergocryptine（DHEC） in human plasma.The analyte was extracted from plasma samples by liquid-liquid extraction,separated through a Shimadzu shim-pack VP-ODS column（150 mm×2.0 mm,5 μm） using isocratic mobile phase consisting of 0.1% formic acid-methanol（48 ∶52）,and analyzed by electro-spray ionization（ESI） in the selected reaction monitoring mode.The precursor to product ion transitions of m/z 594.3→270.0 and m/z 264.1→58.3 were used to measure 8′-OH-DHEC and the IS tramadol,respectively.The method was validated over a concentration range of 50-4 000 pg/mL.The intra-and inter-day precision values were less than 10% and accuracy values 90%-110%.The stability of 8′-OH-DHEC in human plasma under different storage conditions met the requirements of bioanalytical method.The established method was successfully applied to a bioequivalence study after single oral administration of 4 mg DHEC mesilate（test and reference） in 22 healthy volunteers.The 90% confidence intervals of log‐transformed ratios of the cmax and AUC0-t were 89.68%-129.9%,106.9%-121.8%,respectively.The method is selective and suitable for the quantification of 8′-OH-DHEC in human plasma.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2012年第2期177-181,共5页
Journal of China Pharmaceutical University
作者简介
通讯作者Tel：025—83271260E—mail：lxq—cpu@yahoo．com．cn
