液相色谱-串联质谱法测定人血浆中红霉胺的含量

Content determination of erythromycylamine in human plasma by LC-MS-MS

目的建立测定人体内红霉胺血药质量浓度的液相色谱-串联质谱法（LC-MS-MS），为地红霉素药物动力学研究提供方法学依据。方法待测血浆0．5mL用乙醚-二氯甲烷萃取。色谱柱：Zobax XDB C18柱；流动相：甲醇-水-甲酸（体积比80：20：0．5）；流速：0.6mL·min^-1。液相色肾串联质谱采用多反应离子检测，正离子模式。结果血浆中无干扰测定的内源性物质；每个样品分析时间小于4min；线性范围为1．0～1000μg·L^-1，定量下限为1．0μg·L^-1；批内、批间精密度均小于15％。结论LC-MS-MS法可用于红霉胺的临床药物动力学研究。

Objective To develop a sensitive and specific liquid chromatography-tandem mass spectrometry （LC-MS-MS） method for determination of erythromycylamine in human plasma. Methods Erythromycylamine was extracted by diethyl ether and dichloromethane from human plasma, and then separated on a C1s colunto. The mobile phase consisted of methanol-water-formic acid（ V： V： V = 80：20：0.5 ） and the flow rate was 0.6mL·min^-1. A mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. In multiple reaction monitoring（MRM） mode ,the ion combination of m/z 749→m/z 591[M ＋ H]^＋ and m/z 748→m/z 158 [ M ＋ H]^＋ were used to quality erythromycylamine and an internal standard（ clarithromycin）, respectively. Results Chromatograms showed no endogenous interfering peaks in the respective blank human plasma samples. Each analysis was completed within 4 min. The calibra- tion was linear in the concentration range within 1. 0 - 1 000μg·L^-1 and quantitative limit was 1.0μg·L^-1. The intra-batch and inter-batch RSD were less than 15%. Conclusions The method is proved to be suitable for clinical investigation of erythromycylamine pharmacokinetics, which offers advantages of specificity, quickness and higher sensitivity over the previously reported methods.