肾功能亢进患者血浆中亚胺培南浓度 UPLC-MS/MS测定 方法的建立及药代动力学研究.

Objective To establish a ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay to quantify plasma imipenem (IMP) in patients with Augmented Renal Clearance (ARC), and to investigate the pharmacokinetic characteristics of IMP in patients with ARC. Methods The plasma samples were treated with acetonitrile precipitated protein and analyzed by UPLC-MS/MS method with amoxicillin as the internal standard. ARC patients with IMP administration regimen of 1 g, intravenous drip, ARC patients at an interval of 8 h were screened, blood samples were collected at different times and plasma concentrations were detected, and pharmacokinetic parameters were calculated. Results Linear calibration curves of IMP were generated over the range of 0.40-200.00 µg/mL, and the precision, accuracy, matrix effect, method recovery and stabilityall met the requirements. The half-life of IMP in ARC patients was (0.97±0.06)h, the area under the drug curve (AUC) was (48.49±14.93)mg/(Lh), the apparent volume of distribution was (16.15±7.90) L, and the creatinine clearance rate was (18.30±5.70) L/h. The peak con- centration was (15.63±4.60) µg/mL. Conclusion This method has high accuracy and high sensitivity, and can be effectively applied to the detection of IMP concentration in plasma of ARC patients. The metabolic rate and clearance rate of IMP may change in ARC patients, which provides an important reference for clinical drug use. [ABSTRACT FROM AUTHOR]