LC-MS/MSを用いた血漿中カルバペネム系抗菌薬測定系の最適化に関する研究

抄録

Several cases have reported that the plasma concentration of carbapenem antibiotics became lower than expected in patients with critical illness and/or transfusion. Therefore, in order to adjust the doses of carbapenem antibiotics, we developed and optimized the method to measure meropenem (MEPM) and doripenem (DRPM) in human plasma by a liquid chromatography-tandem mass spectrometry (LC-MS/MS). A C18 column and mobile phase consisting of 10 mM ammonium formate containing 0.1％ formic acid in 70％ methanol were used for chromatographic separation. DRPM for MEPM determination and vice versa were used as internal standards. Both MEPM and DRPM could be detected within 5 minutes. Regarding the stock solution, MEPM stock solution should be used within 2 weeks of preparation when stored at -30℃. The solid phase extraction Oasis^® HLB was used to extract carbapenem antibiotics. Thirty mg cartridges were suitable for extraction from 100 μL plasma samples. Importantly, it should be noted that the rate of reduction of MEPM and DRPM in plasma exceeded 20％ two months after freezing at -30℃. Our established method could measure MEPM and DRPM in plasma (1.0-40 μg/mL) that would be useful to adjust their dosages in clinical practice.