title: Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0152 in human plasma using solid-phase extraction.
abstract: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0152 in human plasma to support clinical development. The method consisted of a solid-phase extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray(TM) for analysis. d(7) -GDC-0152 was used as the internal standard. A linear regression (weighted 1/concentration(2) ) was used to fit calibration curves over the concentration range of 0.02-10.0 ng/mL for GDC-0152. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 99.3% with a precision (%CV) of 13.9%. For quality control samples at 0.0600, 2.00 and 8.00 ng/mL, the between-run %CV was ≤8.64. Between-run percentage accuracy ranged from 98.2 to 99.6%. GDC-0152 was stable in human plasma for 363 days at -20°C and for 659 days at -70°C storage. GDC-0152 was stable in human plasma at room temperature for up to 25 h and through three freeze-thaw cycles. In whole blood, GDC-0152 was stable for 12 h at 4°C and at ambient temperature. This validated LC-MS/MS method for determination of GDC-0152 was used to support clinical studies.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, CA 94080, USA. yshin@gene.com
authors.forename: Young G
authors.initials: YG
authors.lastname: Shin
authors.forename: Steve A
authors.initials: SA
authors.lastname: Jones
authors.forename: Stan C
authors.initials: SC
authors.lastname: Murakami
authors.forename: Nageshwar
authors.initials: N
authors.lastname: Budha
authors.forename: Joseph
authors.initials: J
authors.lastname: Ware
authors.forename: Harvey
authors.initials: H
authors.lastname: Wong
authors.forename: Michael H
authors.initials: MH
authors.lastname: Buonarati
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
authors.forename: Cornelis E C A
authors.initials: CE
authors.lastname: Hop
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D003510:Cyclohexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D003510:Cyclohexanes; D011758:Pyrroles; C579046:GDC-0152