高效液相色谱-串联质谱法测定人血浆中多尼培南的浓度

Determination of doripenem concentration in human plasma by liquid chromatography tandem mass spectrometry

目的建立高效液相色谱-质谱联用(LC-MS-MS)法测定人血浆内多尼培南浓度的方法。方法采用Agilent Zorbax C18(2.1mm×150mm,5μm)色谱柱;柱温25℃;流动相为甲醇-水(含10mmol·L-1乙酸铵)(32∶68,V/V);流速为0.2mL·min-1;通过LC-MS-MS,电喷雾离子源(ESI),以多反应监测(MRM)方式进行检测;离子极性监测负离子(-);检测离子为多尼培南m/z419.8[M-H]-→331.4[M-H-C4H7O2]-,法罗培南(内标)m/z284.2[M-H]-→196.1[M-H-C4H7O2]-。结果多尼培南的最低定量限为3.003μg·L-1,线性范围为3.003～10010μg·L-1(r=0.9982)。结论该方法简便、灵敏度高,可以用来进行多尼培南的人体药动学和生物等效性研究。

AIM To establish high-performance liquid chromatographic tandem mass spectrometric method for the determination of doripenem concentration in human plasma. METHODS Agilent Zorbax C18 （2.1 mm × 150 mm, 5 μm） chromatographic column with 25℃ column temperature. The mobile phase consisted of methanol/10 mmol·L^-1 ammonium acetate （32 ： 68, V/V） and flow rate was 0.2 mL·min^-1. A Waters Micromass Quattro micro tandem mass spectrometer equipped with electronic spray ionization source were used as detector and operated in the negative ion mode under multi reaction monitoring （MRM）. The ion of doripenem to detect was m/z 419.8 [M-H]^-→331.4 [M-H-C4H7O2]^- , and the faropenem ion （internal standard） was m/z 284.2 [M-H]-→196.1 [M-H-C4H7O2]^-. RESULTS The lowest qualification limit of doripenem was 3.003 μg·L^-1. The linear concentration range was 3.003 - 10 010 μg·L^-1 with standard correlation coefficient of （r = 0.998 2）.CONCLUSION This method is simple, sensitive, and suitable for clinical pharmacokinetics and bioequivalence studies for doripenem.