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An LC/ESI–MS/MS method to quantify the PI3K inhibitor GDC‐0084 in human plasma and cerebrospinal fluid: Validation and clinical application
Author(s) -
Zhong Bo,
Campagne Olivia,
Tinkle Christopher L.,
Stewart Clinton F.
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4697
Subject(s) - chromatography , calibration curve , chemistry , electrospray ionization , selected reaction monitoring , electrospray , detection limit , cerebrospinal fluid , analytical chemistry (journal) , mass spectrometry , tandem mass spectrometry , medicine
A liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI–MS/MS) method was developed and validated to measure GDC‐0084 in human plasma and cerebrospinal fluid (CSF). Reverse‐phase chromatography with gradient elution was performed using a C 18 column (50 × 2.0 mm, 3 μm). Solid‐phase extraction of plasma and CSF was employed to give excellent recovery. MS detection was performed with positive ion screening in multiple reaction monitoring mode. The precursor to the product ions (Q1 → Q3) selected for GDC‐0084 and GDC‐0084‐ d 6 were 383.2 → 353.2 and 389.2 → 353.2, respectively. A separate calibration curve was established for human plasma and CSF. Both calibration curves, ranging from 0.2 to 200 ng/mL, were linear and had acceptable intra‐ and inter‐day precision and accuracy. The lower limit of quantitation and limit of detection for GDC‐0084 in human plasma were 0.2 ng/mL (signal/noise ≥47) and 0.005 ng/mL (signal/noise ≥3.5), respectively, and for GDC‐0084 in human CSF were 0.2 ng/mL (signal/noise ≥19.7) and 0.04 ng/mL (signal/noise ≥7.2). This method was successfully applied to analyze serial plasma samples obtained from children with diffuse intrinsic pontine gliomas and other midline gliomas who participated in pharmacokinetic studies as part of a phase I clinical trial of GDC‐0084.