Establishment of the quick method to measure plasma cefmetazole by high- performance liquid chromatography and its clinical application

Background Cefmetazole (CMZ) is widely used in Japan as a treatment for urinary tract infections (UTI), intra-abdominal infections, and bacteremia and as an antimicrobial prophylaxis. For the safe use of CMZ, evidence related to pharmacokinetic/pharmacodynamic analyses of CMZ in UTI is necessary. Thus, we attempted to establish a method to quantify CMZ plasma concentration using high-performance liquid chromatography (HPLC) and to verify its clinical application using plasma samples collected from Japanese patients with UTI. Methods Plasma samples were deproteinized by adding acetonitrile (MeCN) containing an internal standard substance (IS), barbital sodium. After centrifugation, the supernatant was collected and evaporated to dryness under a stream of nitrogen gas. The residue was reconstituted with the mobile phase and injected into the HPLC system equipped with a COSMOSIL® 5C ₁₈ -MS-II column. In the mobile phase, 5-mM sodium citrate buffer (pH 3.2)/MeCN (85/15, v/v %) was added at an isocratic flow rate of 1.2 mL/min. CMZ and IS were detected at 272 and 229 nm, respectively, and the total run time was 15 min. The method’s application in clinical samples was evaluated by measuring plasma samples from 23 patients with UTI treated with CMZ. Samples were collected 2–3 h after the initiation of infusion (post-peak level) and 6–24 h after the last dose (trough level). The relationship between plasma CMZ concentrations and creatinine clearance (Ccr) was evaluated. Results The established method was found to have good linearity (0.2–200 µg/mL), precision, and accuracy. Furthermore, our method was applicable to the measurement of plasma in patients with UTI. These results suggest that the established method is suitable for measuring plasma CMZ levels for research to promote the proper use of CMZ. Furthermore, a negative correlation was observed between Ccr and the post-peak level, but not trough levels, of plasma CMZ. Conclusions Our developed method is simple and precise for quantifying plasma CMZ levels and is applicable in clinical settings.