Development and validation of an assay for the measurement of gentamicin concentrations in dried blood spots using UHPLC-MS/MS.

Autor: Anibaletto Dos Santos AL; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Brazil., Cezimbra da Silva AC; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Brazil., Feltraco Lizot LL; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Brazil., Schneider A; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Brazil., Meireles YF; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Brazil., Hahn RZ; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil., Pagnussat LR; Hospital São Vicente de Paulo, Passo Fundo, RS, Brazil., Nonnenmacher JL; Multidisciplinary Residency Program, Universidade de Passo Fundo, RS, Brazil., Hahn SR; College of Pharmacy, Universidade de Passo Fundo, RS, Brazil., Linden R; Analytical Toxicology Laboratory, Universidade Feevale, Novo Hamburgo, RS, Brazil; Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Brazil. Electronic address: rafael.linden@feevale.br.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2022 Jan 20; Vol. 208, pp. 114448. Date of Electronic Publication: 2021 Oct 28.
DOI: 10.1016/j.jpba.2021.114448
Abstrakt: Gentamicin sulfate (GEN) is an aminoglycoside antibiotic with a narrow therapeutic range of plasma concentrations. The collection of venous blood represents a significant burden for patients, especially in neonatology. Dried blood spots (DBS) obtained from capillary blood can be an alternative for drug measurements in this particular population. This study aimed to develop and validate an assay for the quantification of GEN in DBS using UHPLC-MS/MS. Total GEN concentrations were obtained by adding the individual concentrations of the GEN forms C1, C1a, and C2. The assay used a DBS disk containing approximately 17 μL of blood for GEN quantitation in the range of 0.1-40 mg L -1 . Measurement accuracy for total GEN was in the range of 102.6-108.6%, inter-assay precision was 11.3-13.1% and intra-assay precision was 9.1-12.8.% GEN was stable for 21 days at - 20 and 8 °C, but only for 24 h at room temperature. Blood Hct affected the accuracy within acceptable limits (93.8-95% at Hct% of 30, 104.3-113% at Hct% of 50). Blood spotted volume did not affect GEN measurement accuracy. Concentrations of GEN in DBS obtained after heel pricks were correlated to plasma levels in a small cohort of neonatal patients. However, percentual differences between estimated plasma concentrations and actual plasma levels presented values between - 64-35.3% (average difference of - 1.9%). The use of DBS for the measurement of GEN concentrations can increase access to TDM of this antibiotic due to the ease of sample collection and the facilitated specimen transportation logistics when testing is not available onsite.
Competing Interests: Declaration of Competing Interest 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.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: