A highly sensitive and selective UPLC-MS/MS assay for the determination of enarodustat (JTZ-951) in human plasma.

Autor: Pai S; Akros Pharma Inc., 302 Carnegie Center, Suite 300, Princeton, NJ 08540, USA. Electronic address: pai@akrospharma.com., Huang MQ; Akros Pharma Inc., 302 Carnegie Center, Suite 300, Princeton, NJ 08540, USA., Maki K; Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan., Waldron M; PPD Laboratories, 2244 Dabney Road, Richmond, VA 23230, USA., Yoshikawa T; Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan., Keller T; PPD Laboratories, 2244 Dabney Road, Richmond, VA 23230, USA., Burnett J; PPD Laboratories, 2244 Dabney Road, Richmond, VA 23230, USA.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2021 Jun 30; Vol. 1176, pp. 122754. Date of Electronic Publication: 2021 May 13.
DOI: 10.1016/j.jchromb.2021.122754
Abstrakt: Enarodustat, a potent, orally bioavailable, selective inhibitor of hypoxia inducible factor-Prolyl hydroxylase (HIF-PH), has been approved recently in Japan for the treatment of anemia in patients with chronic kidney disease (CKD). To evaluate the pharmacokinetics of enarodustat, a bioanalytical assay in human plasma was needed for the quantitation of enarodustat for both healthy subjects and patients with CKD. The UPLC-MS/MS method for the quantitation of enarodustat was initially validated in a bioanalytical laboratory in Japan to support clinical studies conducted in Japan, and then was transferred and validated in a bioanalytical laboratory in United States to support clinical studies conducted here. A cross-validation was successfully performed between the two bioanalytical laboratories using both quality control (QC) samples and incurred study samples. Enarodustat was fortified with its isotopically labeled internal standard in a 25 µL plasma aliquot and extracted with protein precipitation. The chromatographic separation was achieved on an Acquity UPLC BEH C18 (1.7 µm, 2.1 × 50 mm) column with gradient elution. The calibration curve range for the assay was 1.00-500 ng/mL. Assay precision, accuracy, linearity, selectivity, sensitivity and analyte stability covering sample storage and analysis were established. No interferences were observed from medications that may be co-administered along with enarodustat. The validated UPLC-MS-MS method at the US bioanalytical laboratory has been successfully applied to eight clinical studies for the determination of enarodustat concentrations in human plasma for both healthy subjects and patients with CKD.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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