Affiliation:
1. Volgograd State Medical University
2. Volgograd State Medical University.
Center for Innovative Medicines with Pilot Industrial Production of Volgograd State Medical University.
3. Institute of Continuing Medical and Pharmaceutical Education of Volgograd State Medical University
Abstract
Therapeutic drug monitoring (TDM) is used to increase the individualization of pharmacotherapy, especially in patient groups with a high interindividual variability in pharmacokinetic (PK) parameters. One of these groups of patients is newborn children, for whom drug therapy, especially drugs with a narrow therapeutic range, causes a few difficulties or cannot be used in principle.The aim of the work was to develop and validate quantitative HPLC-MS/MS methods for the determination of vancomycin in “dried blood spot” samples using new protocols and comparison of the results obtained with the results in plasma samples using standard sample preparation methods.Materials and methods. To prepare stock and standard solutions of vancomycin and norvancomycin as an internal standard, dry portions of the corresponding certified standards of vancomycin (Servier, France) and norvancomycin (Augsburg, Germany, purity grade >95.0%) were used. A chromatographic separation of the components was carried out on a Poroshell 120 C18 column (4.6×50 mm, 2.7 µm). When developing conditions for a mass spectrometric detection of the desired substances using the multiple reaction monitoring (MRM) method, precursor ions and their corresponding product ions were determined.Results. A quantitative HPLC-MS/MS method for the determination of vancomycin in «dried blood spot» samples was developed and validated. A comparison was made between vancomycin concentrations in «dried blood spot» samples and plasma samples. Moreover, more than 95% of the calculated average concentrations are within the limits of d-2s and d+2s, which correspond to the values of –10.2 and 12.2. That confirms the suitability of the developed method for the analysis of patient samples.Conclusion. The results obtained make it possible for us to recommend the “dried blood spot” method for therapeutic monitoring of vancomycin, additional studies of PK in this group of patients with subsequent use of this drug in newborns and pediatric patients.
Publisher
Volgograd State Medical University
Reference28 articles.
1. Tolkachev BЕ, Petrov VI, Zayachnikova TЕ, Strygin AV, Anikeev IS, Dotsenko АМ. Therapeutic drug monitoring of vancomycin in neonates: current challenges and perspectives. Lechebnoe Delo. 2021;(2):17–24. DOI: 10.24412/2071-5315-2021-12327
2. Pham JT. Challenges of vancomycin dosing and therapeutic monitoring in neonates. J Pediatr Pharmacol Ther. 2020;25(6):476–84. DOI: 10.5863/1551-6776-25.6.476
3. Tufanova OS, Kasimova AR, Bozhkova SA. Therapeutic drug monitoring for evaluation of the efficacy and safety of vancomycin in patients with orthopaedic infections. Safety and Risk of Pharmacotherapy. 2022;10(2):128–38. DOI: 10.30895/2312-7821-2022-10-2-128-138. Russian
4. Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC Jr, Craig WA, Billeter M, Dalovisio JR, Levine DP. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2009;29(11):1275–9. DOI: 10.1592/phco.29.11.1275
5. Petrov VI, Anikeev IS, Zayachnikova TE, Strygin AV, Dotsenko AM. Adaptation of “dried blood drop” method for therapeutic drug monitoring. Pharmacy & Pharmacology. 2022;10(4):331–42. DOI: 10.19163/2307-9266-2022-10-4-331-342