Determination of 9-nitrocamptothecin by precolumn derivatization and its metabolite 9-aminocamptothecin in a biological fluid using reversed-phase high-performance liquid chromatography with fluorescence detection

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 795; no. 2; pp. 309 - 318
• Main Authors: Zhang, Junhong, Burke, Thomas G, Latus, Lori J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05-10-2003; Elsevier Science
• Subjects: 9-Aminocamptothecin; 9-Nitrocamptothecin; Animals; Antineoplastic agents; Biological and medical sciences; Calibration; Camptothecin - analogs & derivatives; Camptothecin - blood; Chromatography, High Pressure Liquid - methods; Derivatization, LC; Dogs; General aspects; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Fluorescence - methods; 9-Nitrocamptothecin; 9-Aminocamptothecin; Derivatization, LC; Antineoplastic agent; Fissipedia; Biological fluid; Carnivora; Fluorescence detector; Enzyme; DNA topoisomerase; HPLC chromatography; Malignant tumor; Blood plasma; Ovary; Vertebrata; Reversed phase chromatography; Clinical stage; Isomerases; Mammalia; Analysis method; Animal; Advanced stage; Mammary gland; Pancreas; Dog; Quantitative analysis
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/S1570-0232(03)00599-3

A novel insoluble topoisomerase I inhibitor, 9-nitrocamptothecin (9-NC), is in advanced stages of clinical development and has been used to treat a diverse array of tumor types, including breast, ovarian, pancreatic and haematological malignancies. We have established a sensitive high-performance liquid chromatography method using fluorescence detection for the quantitation of 9-NC. Non-fluorescent 9-NC is converted to fluorescent 9-aminocamptothecin (9-AC) via a one-step pre-column derivative reaction. The quantitative limit of 9-NC was 1
ng/ml and the method was reproducible with the respective intra- and inter-day variability falling below 5.0 and 9.0%. The determination of both 9-NC and its metabolite 9-AC in dog plasma was also achieved using the same chromatographic and detection conditions. In dog plasma, the quantitative limits of 9-AC and 9-NC were 0.25 and 1
ng/ml, respectively. The presence of 9-AC in the samples yielded no interference with the determination of 9-NC. However, individual matrices can affect the conversion efficiency of 9-NC, thus indicating that standard samples should be run for each matrix.