Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate ON 01910.Na, a mitotic progression modulator, in human plasma.
A reverse-phase high performance liquid chromatographic method with tandem mass spectrometry (LC-MS/MS) was developed and validated for the quantitation of ON 01910.Na, a novel synthetic benzyl styryl sulfone, in human plasma. The assay involved a simple sample preparation with acetonitrile protein precipitation. ON 01910.Na and the internal standard temazepam were separated on a Waters X-Terra MS C(18) column with mobile phase of acetonitrile containing 0.1% formic acid /10mM ammonium acetate (55:45, v/v) using isocratic flow at 0.2 mL/min for 5 min. The analytes were monitored by tandem-mass spectrometry with electrospray positive ionization. Two calibration curves were generated over the range of 10-2000 ng/mL and 100-20000 ng/mL. The lower limit of quantitation (LLOQ) was 10 ng/mL for ON 01910.Na in human plasma. The accuracy and within- and between-day precisions were within the acceptance criteria for bioanalytical assays. ON 01910.Na was found stable in plasma at -70 degrees C for at least 1 year. The method was successfully applied to characterize the plasma concentration-time profiles of ON 01910.Na in the cancer patients in the Phase I study.
Li
Jing
J
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Zhao
Ming
M
Jimeno
Antonio
A
He
Ping
P
Ramana Reddy
M V
MV
Hidalgo
Manuel
M
Donehower
Ross C
RC
Rudek
Michelle A
MA
D002853:Chromatography, Liquid / Q000379:methods*; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013450:Sulfones / Q000097:blood* / Q000494:pharmacology; D053719:Tandem Mass Spectrometry / Q000379:methods*
D013450:Sulfones; C507134:ON 01910; D005998:Glycine