Quantification of Imipenem and Meropenem in Human Plasma by UPLC-MS/MS and Its Application in Therapeutic Drug Monitoring / 中国药学杂志

ABSTRACT

OBJECTIVE: To develop a sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS /MS) method for simultaneous determination of imipenem and meropenem in human plasma to monitor therapeutic drug concentration. METHODS: The plasma samples were extracted with dichloromethane after precipitated protein by acetonitrile. And then, the analytes were gradient eluted on a UPLC® BEH-C18 (2.1 mm × 50 mm, 1.7 μm) by UPLC-MS /MS with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 300.0→171.0 for imipenem, 384.0→141.0 for meropenem and 390.1→147.0 for meropenem-d6 (internal standard), respectively. RESULTS: Calibration plots were established over the concentration range of 0.39 - 50 μg•mL-1 of imipenem and meropenem, with the lowest detection limit of 0.39 μg•mL-1 using 2 μL sample volumn. Determination of control samples of imipenem and meropenem in plasma validated the LC-MS /MS method. Accuracy, extraction recovery, matrix effect, intra-assay and inter-assay precision all met the requirements. CONCLUSION: This novel method of imipenem and meropenem determination by LC-MS /MS is proven to be a robust protocol that is consistent and reproducible.