Assay of the antiangiogenic compound TNP-470, and one of its metabolites, AGM-1883, by reversed-phase high-performance liquid chromatography in plasma.
This paper describes a reversed-phase, high-performance liquid chromatographic (HPLC) method for the isolation, detection, and quantification of TNP-470 (I) and one of its active metabolites, AGM-1883 (II), from plasma. These compounds are initially extracted from plasma with an organic solvent and then separated from one another on a C18 column. Those fractions eluting from the C18 column and containing either I or II are then derivatized through their epoxide moieties with sodium 8-quinolinethiolate (SQT). This derivatization produces fluorescent species that are isolated and quantified by a second reversed-phase HPLC analysis. The assay yields a lower limit of reliable quantification of 2.5 ng/ml and is linear to a concentration at least as high as 160 ng/ml. The inter-assay percent coefficient of variation is less than 18%.
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Clinical Pharmacokinetics Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Yeh
H J
HJ
Thibault
A
A
Pluda
J M
JM
Itoh
F
F
Yarchoan
R
R
Cooper
M R
MR
D000081:Acetamides / Q000097:blood*; D000903:Antibiotics, Antineoplastic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D003510:Cyclohexanes; D004852:Epoxy Compounds / Q000097:blood; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011804:Quinolines; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood* / Q000737:chemistry; D013141:Spiro Compounds / Q000097:blood*
D000081:Acetamides; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D004852:Epoxy Compounds; D011804:Quinolines; D012717:Sesquiterpenes; D013141:Spiro Compounds; C087809:AGM 1883; C087618:8-mercaptoquinoline; D000077609:O-(Chloroacetylcarbamoyl)fumagillol