Validation of a quantitative multiplex LC-MS/MS assay of carvedilol, enalaprilat, and perindoprilat in dried blood spots from heart failure patients and its cross validation with a plasma assay.

Autor: Joubert A; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Joubert A; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., van der Merwe M; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Norman J; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Castel S; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Denti P; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Sliwa K; Cape Heart Institute, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa., Maartens G; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Sinxadi P; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Wiesner L; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: Journal of mass spectrometry and advances in the clinical lab [J Mass Spectrom Adv Clin Lab] 2022 Dec 12; Vol. 27, pp. 7-17. Date of Electronic Publication: 2022 Dec 12 (Print Publication: 2023).
DOI: 10.1016/j.jmsacl.2022.12.003
Abstrakt: Introduction: Adherence to medication is an important determinant of outcomes in chronic diseases like heart failure. Drug assays provide objective adherence biomarkers. Dried blood spots (DBS) are appealing samples for drug assays due to less demanding transportation and storage requirements.
Objectives: To analytically validate a LC-MS/MS method for the simultaneous quantification of carvedilol, enalaprilat, and perindoprilat in DBS and evaluate the feasibility of using the method as an adherence determining assay. To validate the assay further clinically by establishing correlation and agreement between plasma and DBS samples from a pharmacokinetic pilot study.
Methods: The method was validated over a concentration range of 1.00-200 ng/mL according to FDA guidelines. Adherence tracking ability of the assay was evaluated using a pharmacokinetic pilot study. Correlation and agreement were evaluated through Deming regression and Bland-Altman analysis, respectively.
Results: Accuracy, precision, selectivity, and sensitivity were proven with complete and reproducible extraction recovery at all concentrations tested. Stability of the analytes in the matrix and throughout sample processing was proven. The full range of concentrations of the pharmacokinetic pilot study could be quantified for enalaprilat, but not for carvedilol and perindoprilat. The difference between the observed and calculated plasma concentrations was less than 20 % of their mean for >67 % of samples for all analytes.
Conclusions: The assay is suitable as a screening tool for carvedilol and perindoprilat, while suitable as an adherence determining assay for enalaprilat. Equivalence between observed and predicted plasma concentrations proves DBS and plasma concentrations can be used interchangeably.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2022 THE AUTHORS.)
Databáze: MEDLINE
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