Dried blood spot analysis for the quantification of vancomycin and creatinine using liquid chromatography – tandem mass spectrometry: Method development and validation

• Published in: Clinica chimica acta 2024-01, Vol.553, p.117689-117689, Article 117689
• Main Authors: Bahmany, Soma, Hassanzai, Moska, Flint, Robert B., van Onzenoort, Hein A.W., de Winter, Brenda C.M., Koch, Birgit C.P.
• Format: Article
• Language: English
• Subjects: Antibiotics; Chromatography, High Pressure Liquid - methods; Chromatography, Liquid - methods; Creatinine; Dried blood spot; Dried Blood Spot Testing - methods; Drug Monitoring - methods; Humans; Methicillin-Resistant Staphylococcus aureus; OPAT; Reproducibility of Results; Tandem mass spectrometry; Tandem Mass Spectrometry - methods; Therapeutic drug monitoring; Ultra-high performance liquid chromatography; Vancomycin
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2023.117689

•Dried blood spot (DBS) sampling is a sustainable alternative to venipuncture which can be performed at home.•A highly accurate and rapid assay for the simultaneous quantification of vancomycin and creatinine in DBS using LC-MS/MS was successfully developed and validated.•Hematocrit levels between 0.3 and 0.5 L/L do not affect the accuracy of vancomycin and creatinine measurements in DBS.•Vancomycin and creatinine are stable in DBS at room temperature and in the freezer −20 °C for at least four weeks. Vancomycin is a widely used antibiotic for the treatment of gram-positive bacterial infections, especially for methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to a small therapeutic range and large inter-patient variability, therapeutic drug monitoring (TDM) of vancomycin is required to minimize toxicity and maximize treatment efficacy. Venous blood sampling is mostly applied for TDM of vancomycin, although this widely used sampling method is more invasive compared to less painful alternatives, such as the dried blood spot (DBS) method, which can be performed at home. We developed an UPLC-MS/MS method for the quantification of vancomycin and creatinine in DBS. A fast sample preparation and short analysis run time of 5.2 min were applied, which makes this method highly suitable for clinical settings. Validation was performed according to international (FDA and EMA) guidelines. The validated concentration range was found linear for creatinine from 41.8 µmol/L to 722 µmol/L and for vancomycin from 3.8 mg/L to 76.6 mg/L (r2 > 0.990) and the inaccuracies, imprecisions, hematocrit effects, and recoveries were