Sensitive high-performance liquid chromatographic fluorescence assay for the quantitation of topotecan (SKF 104864-A) and its lactone ring-opened product (hydroxy acid) in human plasma and urine |
| |
Authors: | WJ Loos G Stoter J Verweij JHM Schellens |
| |
Institution: | Laboratory of Experimental Chemotherapy and Pharmacology, Department of Medical Oncology, Rotterdam Cancer Institute/ University Hospital Rotterdam, P.O. Box 5201, 3008 AE Rotterdam, Netherlands |
| |
Abstract: | A sensitive reversed-phase high-performance liquid chromatographic fluorescence method is described for the simultaneous determination of topotecan (I) and the hydrolysed lactone ring-opened product hydroxy acid (II) in plasma and for the determination of I in urine. To 250 μl of plasma, a 750-μl volume of cold methanol was added to stabilize the pH-dependent conversion of I into II. In plasma, the lower limit of quantitation (LLQ) for both compounds was 0.10 ng/ml. The between-day variation for I at the LLQ was 7.1% and for II was 5.5%. Prior to injection, urine samples were acidified with orthophosphoric acid and diluted with phosphate-buffered saline (PBS). In urine, the calibration curve for I was linear in the range of 10 to 250 ng/ml and the LLQ was 10 ng/ml. The assay was developed to enable pharmacological analysis of I, in on-going phase I and II studies, in patients with solid tumors. |
| |
Keywords: | Topotecan |
本文献已被 ScienceDirect 等数据库收录! |
|