Simultaneous determination of vancomycin and creatinine in plasma applied to volumetric absorptive microsampling devices using liquid chromatography-tandem mass spectrometry.

Vancomycin (VCM) is a glycopeptide antibiotic, widely used against methicillin-resistant Staphylococcus aureus infections, and its clearance is highly correlated to creatinine (CRE) clearance. Usually, VCM and CRE levels are measured in serum or plasma specimens obtained from venous blood, after phlebotomy. As the majority of hospitals in Developing Countries do not have on-site access to VCM measurements, the availability of data on patient's VCM levels would involve the transport of liquid samples to specialized laboratories. An alternative to overcome the logistic difficulties of liquid biological specimens is the use of dried microsamples, such as plasma applied to volumetric absorptive microsampling (VAMS) devices. The aim of this study was to develop and validate a LC-MS/MS assay for the simultaneous determination of VCM and CRE in plasma applied to VAMS devices. VCM and CRE levels were determined in clinical relevant ranges with acceptable precision and accuracy and both compounds were stable in VAMS for up to two weeks at 45 °C. Concentrations measured in VAMS differed from those measured in plasma and the use of estimation approaches was necessary to estimate plasma concentrations. VCM levels in plasma can be estimated by multiplying VAMS measurements by the correction factor of 0.934. The unbiased estimation of CRE plasma levels from VAMS required the use of the equation CRE = 0.9808 * CRE + 1.6621. VAMS can be used as an alternative for short-term storage and transportation of plasma at ambient and high temperatures, allowing a more widespread access to VCM therapeutic drug monitoring in limited-resources settings.