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采用改进、可靠、灵敏的LC-ESI-MS/MS方法测定人体血清中咪唑立宾浓度,内标为甲砜霉素。乙腈沉淀血清中蛋白后经过HPLC反相C18色谱柱分离,流动相为0.1%醋酸铵水溶液-甲醇(47∶53);质谱检测采用MRM(多级反应检测)模式,咪唑立宾和内标的离子对(母离子/子离子)分别为258.2/126.0和354.1/185.2。咪唑立宾测定浓度在0.02～2μg·mL-1内呈良好线性,定量限为0.02μg·mL-1,精密度和准确度可靠。本方法成功应用于中国健康志愿者生物等效性研究,单剂量口服咪唑立宾100mg试验制剂和参比制剂药代动力学参数如下:Cmax为1.00±0.21和1.00±0.22μg·mL-1;AUC0-∞为6.72±1.39和6.48±1.44μg·h·mL-1;t1/2为2.77±0.26和2.66±0.29h;tmax为2.95±0.78和2.84±0.50h。
The concentration of mizoribine in human serum was determined by an improved, reliable and sensitive LC-ESI-MS / MS method. The internal standard was thiamphenicol. The protein in serum was precipitated by acetonitrile and the residue was separated on a reversed-phase HPLC C18 column. The mobile phase consisted of 0.1% ammonium acetate-methanol (47:53). Mass spectrometry was performed with MRM (multi-step reaction assay) (Parent ions / daughter ions) were 258.2 / 126.0 and 354.1 / 185.2, respectively. The determination of mizoribine linear within 0.02 ~ 2μg · mL-1, the limit of quantification was 0.02μg · mL-1, the precision and accuracy were reliable. The method was successfully applied to the bioequivalence study of healthy volunteers in China. The pharmacokinetic parameters of the test preparation and the reference preparation of the single dose of mizoribine 100mg were as follows: Cmax 1.00 ± 0.21 and 1.00 ± 0.22μg · mL-1; AUC0-∞ was 6.72 ± 1.39 and 6.48 ± 1.44 μg · h · mL-1; t1 / 2 was 2.77 ± 0.26 and 2.66 ± 0.29 h; tmax was 2.95 ± 0.78 and 2.84 ± 0.50 h.