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Determination of a novel antifibrotic small molecule GDC-3280 in human plasma and urine by liquid chromatography tandem mass spectrometry to support its first-in-human clinical trial.
Wang, Jianshuang; Van Parys, Michael; Pan, Lin; Chen, Yuan; Cheung, Dorothy; McKnight, Janine; Milanowski, Dennis; Ding, Xiao; Dean, Brian.
Afiliación
  • Wang J; Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, CA, USA.
  • Van Parys M; Department of Bioanalytical Chemistry, Covance Laboratories Inc., Madison, WI, USA.
  • Pan L; Department of Clinical Pharmacology, Genentech Inc, South San Francisco, CA, USA.
  • Chen Y; Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, CA, USA.
  • Cheung D; Department of Early Clinical Development, Genentech Inc, South San Francisco, CA, USA.
  • McKnight J; Department of Bioanalytical Chemistry, Covance Laboratories Inc., Madison, WI, USA.
  • Milanowski D; Department of Bioanalytical Chemistry, Covance Laboratories Inc., Madison, WI, USA.
  • Ding X; Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, CA, USA.
  • Dean B; Department of Drug Metabolism and Pharmacokinetics, Genentech Inc., South San Francisco, CA, USA.
Biomed Chromatogr ; 33(4): e4482, 2019 Apr.
Article en En | MEDLINE | ID: mdl-30618197
A specific and robust LC-MS/MS method was developed and validated for the quantitative determination of GDC-3280 in human plasma and urine. The nonspecific binding associated with urine samples was overcome by the addition of CHAPS. The sample volume was 25 µL for either matrix, and supported liquid extraction was employed for analyte extraction. d6-GDC-3280 was used as the internal standard. Linear standard curves (R2 > 0.9956) were established from 5.00 to 5000 ng/mL in both matrices with quantitation extended to 50,000 ng/mL through dilution. In plasma matrix, the precision (RSD) ranged from 1.5 to 9.9% (intra-run) and from 2.4 to 7.2% (inter-run); the accuracy (RE) ranged from 96.1 to 107% (intra-run) and from 96.7 to 104% (inter-run). Similarly, in urine the precision was 1.5-6.2% (intra-run) and 1.9-6.1% (inter-run); the accuracy was 83.1-99.3% (intra-run) and 87.1-98.3% (inter-run). Good recovery (>94%) and negligible matrix effect were achieved in both matrices. Long-term matrix stability was established for at least 703 days in plasma and 477 days in urine. Bench-top stability of 25 h and five freeze-thaw cycles were also confirmed in both matrices. The method was successfully implemented in GDC-3280's first-in-human trial for assessing its pharmacokinetic profiles.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridonas / Cromatografía Liquida / Espectrometría de Masas en Tándem Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Biomed Chromatogr Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridonas / Cromatografía Liquida / Espectrometría de Masas en Tándem Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Biomed Chromatogr Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido