液质联用检测人体血浆中的阿奇霉素

Determination of Azithromycin in Human Plasma by High Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry

采用高效液相色谱串联质谱技术（HPLC—MS／MS）测定人体血浆中阿奇霉素的浓度．选用LichrospherCN柱，流动相为V（乙腈）：V（水）=40：60（水中含体积分数为0．1％的甲酸和质量分数为0．1％的醋酸铵），电喷雾离子源正离子方式检测．该方法在2．34—600ng/mL范围内线性关系良好，定量下限为2．34ng/mL（S／N〉10），回收率94．13％～97．42％，基质效应92．50％～107．87％，日内和日间测定药物浓度的相对标准偏差（RSD）均小于10．O％．用该方法测定了24名男性健康志愿者单剂量口服500mg阿奇霉素试剂和参比制剂于192h内的血药浓度，并进行了生物等效性研究．

A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated for determination of azithromycin in human plasma with erythromycin as the internal stan-dard. Chromatographic separation was performed on a Lichrospher CN column（4.6 mm× 150 mm） with a mixture of acetonitrile and water （ containing 0. 1% formic acid and 0. 1% ammonium acetate, volume ratio 40： 60 ） as mobile phase. Selected ion monitoring was specific for azithromycin and erythromycin （IS）. The assay was linear over the mass concentration range 2.34-600 ng/mL and the correlation coefficients for the calibration curves ranged from 0. 997 to 0. 999. The intra- and inter-day precisions, calculated from quality control samples, were less than 10%. Protein precipitation with methanol was chosen for sample preparation method. The recoveries ranged from 94. 13% to 97.04 % and matrix effect ranged from 92. 50% to 107.87%. The method was applied to bioequivalence study after oral administration of 500 mg azithromycin to 24 healthy volunteers.