Simultaneous determination of OSI-774 and its major metabolite OSI-420 in human plasma by using HPLC with UV detection.
A new method was developed and validated for quantitating OSI-774 and its metabolite OSI-420 in human plasma. Sample preparation involved initial extraction with methyl t-butyl ether followed by back extraction with HCl and re-extraction with methyl t-butyl ether. This extraction process resulted in significant improvement in the specificity, reproducibility and sensitivity. The analytes were separated on a Water Symmetry C18 analytical column and the mobile phase consisted of acetonitrile-0.05 M potassium phosphate buffer (42:58, v/v) (pH 4.8), and monitored at a wavelength 345 nm. Values of between- and within-day precision and accuracy for both OSI-774 and OSI-420 were <20%. This method was successfully applied to study steady-state pharmacokinetics of OSI-774 and OSI-420 in a phase II clinical trial.
Zhang
Wenjiang
W
Department of Experimental Therapeutics, Ontario Cancer Institute, Ontario, Canada.
Siu
Lillian L
LL
Moore
Malcolm J
MJ
Chen
Eric X
EX
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D011799:Quinazolines / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
C487471:OSI-420; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors