Determination of vancomycin in serum by liquid chromatography–high resolution full scan mass spectrometry

A liquid chromatography–mass spectrometry (LC–MS) method was developed for the analysis of vancomycin (VCM) in human serum. The method was based on full scan data with extracted ions for the accurate masses of VCM and the atenolol internal standard obtained by Fourier transform MS. VCM was extracted from serum using strong cation exchange (SCX) solid phase extraction (SPE). The method was found to be linear in the range 0.05–10 μg/ml, which was adequate for quantification of VCM in serum samples, with a limit of quantification (LOQ) of 0.005 μg/ml and a limit of detection (LOD) of 0.001 μg/ml. Intra-day precision (n = 5) was ±3.5%, ±2.5%, ±0.7% at 0.05, 0.5 and 5 μg/ml, respectively. Inter-day precision (n = 5) was ±7.6%, ±6.4%, ±3.9% at 0.05, 0.5 and 5 μg/ml, respectively. The process efficiency for VCM was in the range 89.2–98.1% with the recovery for the atenolol internal standard (IS) being 97.3%. The method was used to determine VCM levels in patients during peri-operative infusion of the drug, which was found to result in drug levels within the required therapeutic window.