Adaptation of “dried blood drop” method for therapeutic drug monitoring

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Abstract

To control the concentration of drugs with a narrow therapeutic range, and to conduct effective and safe treatments, Therapeutic Drug Monitoring (TDM) is carried out. However, to date, the implementation of TDM is associated with various difficulties, for the solution of which more convenient and less invasive methods for collecting biological material are being developed.

The aim of the study was to develop protocols for the collection and storage of “dried blood spot” (DBS) samples, as well as protocols for the validation methods for the quantitative determination of drugs in whole blood, using this technology for subsequent therapeutic drug monitoring.

Materials and methods. To analyze a “dried blood spot” method in detail and to identify the characteristic features of taking and storing biosamples, a collection and analysis of scientific literature over the past 10 years has been conducted. The search for literature materials has been carried out from open and accessible sources located in the scientific libraries of institutions, in electronic databases and search engines: Elibrary, PubMed, Scopus, Cyberleninka, Medline, ScienceDirect, Web of Science, Google Scholar. Primary protocols for taking, storing and analyzing samples of the “dried blood drop” have been prepared. To obtain the adequate quality samples, the developed protocols have been tested and optimized at the stages of selection and storage. By high-performance liquid chromatography with mass spectrometric detection (HPLC-MS/MS), using a “dried blood drop” as a sample preparation, drug validation protocols have been optimized to ensure that acceptable validation characteristics were achieved, and subsequent Therapeutic Drug Monitoring was performed.

Results. The features of the collection, storage and analysis of the “dried blood spot” samples have been revealed. Such characteristics as a spot volume effect, a hematocrit effect, a droplet uniformity, which can affect the results of a quantitative HPLC-MS/MS analysis, have been determined. For a successful use of the new methods, appropriate protocols for taking samples of “dried blood spot” from the finger of adult patients and from the heel of newborns, as well as protocols for validating methods for the quantitative determination of drugs from these samples, have been developed.

Conclusion. The application of the “dried blood spot” method using newly developed protocols for taking, storing and analyzing biological samples, relieves the existing constraints in conducting TDM, and can later become a promising method for conducting preclinical and clinical studies.

About the authors

Vladimir I. Petrov

Volgograd State Medical University; Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University

Author for correspondence.
Email: brain@sprintnet.ru
ORCID iD: 0000-0002-0258-4092

Doctor of Sciences (Medicine), Professor, Academician of the Russian Academy of Sciences; Head of the Department of Clinical Pharmacology and Intensive Care, Volgograd State Medical University; director of Scientific Centre of Innovative Medicines with Pilot Production, Volgograd State Medical University;Chief freelancespecialist – a clinical pharmacologist of the Ministry of Health of the Russian Federation; Honored Scientist of the Russian Federation; Honored Doctor of the Russian Federation

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 39, Novorossiyskaya Str., Volgograd, 400087

Ivan S. Anikeev

Volgograd State Medical University; Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University

Email: anikeivan@yandex.ru
ORCID iD: 0000-0002-9384-4338

post-graduate student, Department of Clinical Pharmacology and Intensive Care, Volgograd State Medical University; Head of the Laboratory of Pharmacokinetics, Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 39, Novorossiyskaya Str., Volgograd, 400087

Tatyana E. Zayachnikova

Institute for Continuing Medical and Pharmaceutical Education, Volgograd State Medical University

Email: guz5deti@mail.ru
ORCID iD: 0000-0001-6758-4686

Candidate of Sciences (Medicine), Associate Professor, Professor of the Department of Pediatrics and Neonatology, Institute of Continuous Medical and Pharmaceutical Education, Volgograd State Medical University

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131

Andrey V. Strygin

Volgograd State Medical University; Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University; Volgograd Medical Research Center

Email: drumsav@mail.ru
ORCID iD: 0000-0002-6997-1601

Candidate of Sciences (Medicine), Associate Professor, Head of the Department of Fundamental Medicine and Biology, Volgograd State Medical University; Deputy Director of Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University; Head of the Laboratory of Genomic and Proteomic Research,Volgograd Medical Research Center

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 39, Novorossiyskaya Str., Volgograd, 400087; 1, Pavshikh Bortsov Sq., Volgograd, 400131

Anna M. Dotsenko

Volgograd State Medical University; Volgograd Medical Research Center

Email: ev8278@mail.ru
ORCID iD: 0000-0003-3324-3351

Assistant of the Department of Fundamental Medicine and Biology, Volgograd State Medical University; Junior Researcher, Laboratory of Genomic and Proteomic Research,Volgograd Medical Research Center

Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 1, Pavshikh Bortsov Sq., Volgograd, 400131

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Supplementary files

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2. Figure 1 – Puncture location of newborn’s heel

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3. Figure 2 – Example of a map for DBS

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4. Figure 3 – Mass spectrum of ivabradine in blood plasma

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5. Figure 4 – Chromato-mass spectrogram of ivabradine in blood plasma

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Copyright (c) 2023 Petrov V.I., Anikeev I.S., Zayachnikova T.E., Strygin A.V., Dotsenko A.M.

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