LC-MS/MS法同时测定人血浆中佐芬普利及活性代谢物佐芬普利拉  

Liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of zofenopril and its active metabolite zofenoprilat in human plasma

作　　者：曹静[1] 田媛 汪浩[1] 

机构地区：[1]南京市疾病预防控制中心理化科,江苏南京210003 [2]中国药科大学分析测试中心,江苏南京210009

出　　处：《现代预防医学》2017年第23期4335-4337,共3页Modern Preventive Medicine

摘　　要：目的建立人血浆中佐芬普利及活性代谢物佐芬普利拉的LC-MS/MS同时测定方法。方法血浆样品加入1,4-二硫苏糖醇(DTT)作为稳定剂保护佐芬普利拉的活性巯基,于酸性条件下采用甲基叔丁基醚进行提取浓集,地西泮作为内标,采用C_8(2.1×150 mm I.D.,3.5μm)柱分离,流动相为甲醇:0.1%甲酸=85∶15(v/v),流速:0.2 ml/min,柱温:30℃;ESI选择性反应正离子方式进行检测,内标法定量。结果佐芬普利在0.20~800 ng/ml范围内线性关系良好,r=0.995 4,最低检出限为0.1 ng/ml,批内、批间精密度分别为1.00%~6.06%及3.66%~5.97%;佐芬普利拉在0.50-2 000 ng/ml范围内线性关系良好,r=0.999 4,最低检测限为0.25 ng/ml,批内、批间精密度分别为0.91%~7.05%及2.92%~7.29%。结论本法简单、灵敏、准确,可用于血浆中佐芬普利及其活性代谢物佐芬普利拉的测定。Objective To establish a rapid LC - MS/MS method for simultaneous determination of zofenopril and its active metabolite zofenoprilat in human plasma. Methods In plasma samples, 1,4 - dithiothreitol （DTY） was added as a stabilizer to protect the thiol group of zofenoprilat, and diazepam was used as internal standard （IS）. The plasma samples were liquid - liquid extracted with methyl tert -butyl ether in acid medium,then separated on C8 column （2.1×150 mm I.D.,3.5μm） and detected by triple - quadruple tandem mass spectrometer in the selected reaction monitoring （SRM） mode. Methanol and 0.1% formic acid solution （85：15, v/v） were used as mobile phase, with a flow rate of 0.2 ml/min. Results The linear range of zofenopril was 0.20 - 800 ng/ml with r = 0. 995 4, and the limit of detection was 0. 1 ng/ml. The intra - and inter - batch standard deviations were in the range of 1.00%- 6.06% and 3.66% ~ 5.97%, respectively. The linear range of zofenoprilat was 0.50 - 2 000 ng/ml with r = 0. 999 4, and the limit of detection was 0.25 ng/ml. The intra - and inter - batch standard deviations were in the range of 0.91% - 7.05% and 2.92% - 7.29%, respectively. Conclusion The method is simple and sensitive, which makes it suitable for determination of zofenopril and zofenoprilat in human plasma.

关 键 词：LC-MS/MS 佐芬普利 佐芬普利拉 人血浆 

分 类 号：R118[医药卫生—公共卫生与预防医学]