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J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Aug 15;1028:25-32. doi: 10.1016/j.jchromb.2016.05.050. Epub 2016 Jun 3.

An aqueous normal-phase chromatography coupled with tandem mass spectrometry method for determining unbound brain-to-plasma concentration ratio of AZD1775, a Wee1 kinase inhibitor, in patients with glioblastoma.

Author information

1
Karmanos Cancer Institute, Wayne State University, Detroit, MI, 48201, USA.
2
Barrow Neurological Institute, St. Joseph's Hospital & Medical Center, Phoenix, AZ, 85013, USA.
3
Yale Cancer Center, Yale School of Medicine, New Haven, CT, 06520, USA.
4
Karmanos Cancer Institute, Wayne State University, Detroit, MI, 48201, USA. Electronic address: lijin@karmanos.org.

Abstract

A rapid, sensitive, and robust aqueous normal-phase chromatography method coupled with tandem mass spectrometry was developed and validated for the quantitation of AZD1775, a Wee-1 inhibitor, in human plasma and brain tumor tissue. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on ethylene bridged hybrid stationary phases (i.e., Waters XBridge Amide column) under an isocratic elution with the mobile phase consisting of acetonitrile/ammonium formate in water (10mM, pH 3.0) (85:15,v/v) at a flow rate of 0.8mL/min for 5min. The lower limit of quantitation (LLOQ) was 0.2ng/mL of AZD1775 in plasma and tissue homogenate. The calibration curve was linear over AZD1775 concentration range of 0.2-1000ng/mL in plasma and tissue homogenate. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method (<15%). The method was successfully applied to assess the penetration of AZD1775 across the blood-brain tumor barrier, as assessed by the unbound brain-to-plasma ratio, in patients with glioblastoma.

KEYWORDS:

AZD1775; Aqueous normal-phase chromatography; Fraction unbound; LC–MS/MS; Tandem mass spectrometry; Unbound brain-to-plasma ratio

PMID:
27318641
DOI:
10.1016/j.jchromb.2016.05.050
[Indexed for MEDLINE]

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