Quantitation of TNP-470 and its metabolites in human plasma: sample handling, assay performance and stability.
A selective and sensitive assay for the determination of TNP-470 and two of its metabolites, AGM-1883 and M-II, in human plasma was developed. The assay involved liquid-liquid extraction followed by analysis using high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. Because TNP-470 is most stable in a pH of 4-5, an acidification procedure was utilized to prevent degradation of TNP-470 during sample collection which involved acidifying the whole blood sample collected with 5 mg of citric acid per ml of blood. Liquid-liquid extraction using an organic solvent mixture was chosen over solid-phase extraction to minimize the degradation of TNP-470 during solvent evaporation.
Drug Metabolism, Abbott Laboratories, Abbott Park, IL 60064, USA.
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D000081:Acetamides / Q000097:blood*; D000903:Antibiotics, Antineoplastic / Q000097:blood*; D001800:Blood Specimen Collection; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003510:Cyclohexanes; D004355:Drug Stability; D005069:Evaluation Studies as Topic; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood*; D013048:Specimen Handling; D013141:Spiro Compounds / Q000097:blood*
D000081:Acetamides; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D013141:Spiro Compounds; C087809:AGM 1883; D000077609:O-(Chloroacetylcarbamoyl)fumagillol