Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7615894 | Journal of Chromatography B | 2016 | 8 Pages |
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 (10Â mM, pH 3.0) (85:15,v/v) at a flow rate of 0.8Â mL/min for 5Â min. The lower limit of quantitation (LLOQ) was 0.2Â ng/mL of AZD1775 in plasma and tissue homogenate. The calibration curve was linear over AZD1775 concentration range of 0.2-1000Â ng/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.
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Jianmei Wu, Nader Sanai, Xun Bao, Patricia LoRusso, Jing Li,