Analytical and clinical validation of a dried blood spot assay for the determination of paclitaxel using high-performance liquid chromatography-tandem mass spectrometry

Autor(es):Mostrar menos -

Andriguetti, Natalia B. ^{[1, 2]} ; Hahn, Roberta Z. ^{[1, 2]} ; Lizot, Lilian F. ^{[1, 2]} ; Raymundo, Suziane ^{[1, 2]} ; Costa, Jose L. ^{[3, 4]} ; da Cunha, Kelly F. ^[4] ; Vilela, Ramon M. M. ^[5] ; Kluck, Helena M. ^[6] ; Schwartsmann, Gilberto ^{[6, 7]} ; Antunes, Marina V. ^{[1, 2]} ; Linden, Rafael ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Feevale, Lab Analyt Toxicol, Novo Hamburgo, RS - Brazil

^[2] Univ Feevale, Grad Program Toxicol & Analyt Toxicol, Novo Hamburgo, RS - Brazil

^[3] Univ Estadual Campinas, Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Campinas Poison Control Ctr, Campinas, SP - Brazil

^[5] Univ Fed Ciencias Saude Porto Alegre, Porto Alegre, RS - Brazil

^[6] Univ Fed Rio Grande do Sul, Porto Alegre, RS - Brazil

^[7] Hosp Clin Porto Alegre, Oncol Serv, Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL BIOCHEMISTRY; v. 54, p. 123-130, APR 2018.
• Citações Web of Science: 3

Resumo

Background: Paclitaxel (PCT) is a chemotherapeutic drug widely used for the treatment of several types of tumors, and its use is associated with severe adverse events, mainly neurologic and hematopoietic toxicities. The relation between systemic exposure and clinical response to PCT was previously described, making paclitaxel a potential candidate for therapeutic drug monitoring (TDM). The use of dried blood spot (DBS) sampling could allow complex sampling schedules required for TDM of PCT. The aim of this study was to develop and validate an LC-MS/MS assay for the quantification of PCT in DBS. Methods: PCT was extracted from one 8 mm DBS punch with a mixture of methanol and acetonitrile, followed by chromatographic separation in a Kinetex C18 (50 x 4.6 mm, 2.6 mu m) column. Detection was performed in a 5500-QTRAP (R) mass spectrometer, with a run time of 2.3 min. Results: The assay was linear in the range of 2.5 to 400 ng mL(-1). Precision (CV%) and accuracy at the concentration levels of 7.5, 40 and 150 ng mL(-1) were 1.69-4.9% and 106.25 to 109.92%, respectively. PCT was stable for 21 days at 25 and 45 degrees C. The method was applied to DBS samples obtained from 34 patients under PCT chemotherapy. The use of a simple correction factor, derived from the correlation between PCT concentrations in plasma and DBS in this set of patients, allowed unbiased estimation of PCT plasma concentrations from DBS measurements, with similar clinical decisions using either plasma or DBS measurements. Conclusions: DBS testing of PCT concentrations represents a promising alternative for the dissemination of PCT dose individualization. (AU)

• Processo FAPESP: 15/10650-8 - Estudo da estabilidade de fármacos, drogas de abuso e praguicidas em amostras de sangue seco em papel, e sua aplicação na toxicologia forense
• Beneficiário: José Luiz da Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular