Development and validation of a method for quantitation of ce-fepime/avibactam in M-H broth:application to antibacterial activity using in vitro PK/PD Model
AIM:To establish a method for quanti-tation of cefepime and avibactam in M-H broth,and applicated in the in vitro dynamic PK/PD mod-el.METHODS:The cefepime was also determined using the high-performance liquid chromatography method(HPLC),the avibactam was also determined using the liquid chromatography-mass spectrome-try(LC-MS/MS),an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae(CRKP).RESULTS:The linear ranges of cefepime and avibactam were good at(0.5-20)and(0.1-25)μg/mL(r=0.999),and the low-er limit concentrations were 0.5 and 0.1 μg/mL.The extraction recoveries of cefepime and avibac-tam in M-H broth were 88.0％-101.7％and 90.9％-95.2％,the relative standard deviation of intra-day precision and inter-day precision were less than 5.2％.The concentration-time curves were well sim-ulated by the PK/PD model.All observed concentra-tions in each experiment were in the range of 20％of the targeted values.For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL,the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mLat the cefepime/avibactam 2.5 g q8 h administration after 24 h.CONCLUSION:The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability.For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.
cefepimeavibactamHPLCLC-MS/MSin vitro dynamic PK/PD model
国家科技期刊平台
NSTL
万方数据
维普
