High-performance liquid chromatographic method for the determination of a novel thymidylate synthase inhibitor, AG 331, in human serum.
AG 331 is a novel thymidylate synthase inhibitor currently in Phase I clinical trial. To determine the pharmacokinetic parameters of AG 3331 in human subjects, a suitable analytical method was developed using high-performance liquid chromatography. Serum and urine samples were prepared using both solid-phase extraction and solvent extraction. Either 4,4'-diaminodiphenyl sulfone or benz[cd]indole-2(1H)-one were used as internal standards for the method. A reversed-phase C18 analytical column completely resolved the drug and internal standard peaks from non-specific substances present in biological matrix. The method was validated for precision, accuracy, and reproducibility in serum and was linear over a concentration range of 50-2000 ng/ml, with a limit of detection of 20.0 ng/ml and a quantifiable limit of 50 ng/ml.
Li
W Y
WY
Department of Pharmaceutical Sciences, School of Pharmacy, University of southern California, Los Angeles 90033, USA.
Chatterjee
D J
DJ
Shetty
B V
BV
Wu
E Y
EY
Muggia
F
F
Koda
R T
RT
D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004791:Enzyme Inhibitors / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007211:Indoles; C087748:AG 331; D013940:Thymidylate Synthase