A UHPLC–MS/MS method for the simultaneous determination of vancomycin, norvancomycin, meropenem, and moxalactam in human plasma and its clinical application

We developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine four antibacterial drugs in human plasma for clinical usage. Samples were prepared using protein precipitation with methanol. Chromatographic separation was accomplished in 4.5 min on a BEH C18 column (2.1 × 50 mm, 1.7 μm) using a gradient elution of methanol and water (containing 7.71 g/L concentrated ammonium acetate, adjusted to pH 6.5 with acetic acid) at a flow rate of 0.4 mL/min. Positive electrospray was used for ionization. The method was linear in the concentration range 1-100 μg/mL for vancomycin, norvoncomycin, and meropenem; and 0.5-50 μg/mL for R-isomer of moxalactam and S-isomer of moxalactam. For all analytes, the intra- and inter-day accuracies and precisions were -8.47%-10.13% and less than 12%, respectively. The internal standard normalized recoveries and matrix effect were 62.72%-105.78% and 96.67%-114.20%, respectively. All analytes were stable at six storage conditions, with variations of less than 15.0%. The method was applied in three patients with central nervous system infection. The validated method might be useful for routine therapeutic drug monitoring and pharmacokinetic study.