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.
����ѩ, ������, ����, ����÷, ��, ������. ��Ѫ�����ǰ����Ϻ��������ϵ�UPLC-MS/MS������������������ҩ����[J]. �й�ҩѧ��־, 2018, 53(3): 218-222.
WANG Xiao-xue, CHEN Wen-qing, KONG Xu-dong, LI Peng-mei, CUI Gang, ZHANG Xiang-lin. Quantification of Imipenem and Meropenem in Human Plasma by UPLC-MS/MS and Its Application in Therapeutic Drug Monitoring. Chinese Pharmaceutical Journal, 2018, 53(3): 218-222.
IKEDA K, IKAWA K, MORIKAWA N, et al. High-performance liquid chromatography with ultraviolet detection for real-time therapeutic drug monitoring of meropenem in plasma[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2007, 856(1-2):371-375.
[2]
KULKARNI M V, TICHY A N, PYKA J S, et al. Use of imipenem to detect KPC, NDM, OXA, IMP, and VIM carbapenemase activity from gram-negative rods in 75 min using liquid chromatography-tandem mass spectrometry [J]. J Clin Microbiol, 2014,52(7): 2500-2505.
[3]
KOAL T, DETERS M, RESCH K, et al. Quantification of the carbapenem antibiotic ertapenem in human plasma by a validated liquid chromatography-mass spectrometry method[J]. Clin Chim Acta, 2006, 364(1-2): 239-245.
[4]
MARTENS L J, BODE S M. Quantification of meropenem in human plasma by HILIC-tandem mass spectrometry [J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2017, 1(1046):13-17.
[5]
KONG W H,JU H S,WANG X X,et al. Determination of imipenem, meropenem, panipenem, faropenem concentrations in human plasma by HPLC [J]. Chin Pharm J (�й�ҩѧ��־), 2014, 49(14): 1247-1251.
[6]
COTE C L, BERGERON A, MESS J N, et al. Matrix effect elimination during LC-MS/MS bioanalytical method development [J]. Bioanalysis, 2009, 1(7):1243-1257.
[7]
LIU H, WANG H W, QIU S L. Study of peak profile of carbapenem antibiotics in HPLC ��. Peak broadening and splitting of imipenem [J]. Chin J Antibiotics (�й���������־), 2003, 28(8): 468-474.
[8]
DRUSANO G L. Prevention of resistance: a goal for dose selection for antimicrobial agents [J]. Clin Infect Dis, 2003, 36(suppl 1):42-50.
[9]
TAM V H, MC K P S, AKINS R L, et al. Pharmacodynamics of cefepime in patients with Gram-negative infections [J]. J Antimicrob Chemother, 2002, 50(3): 425-428.
2018, Vol. 53 
