Determination of the two diastereoisomers of lobaplatin (D-19466) in plasma ultrafiltrate of cancer patients with a normal or an impaired kidney or liver function by high-performance liquid chromatography with ultraviolet detection.
Lobaplatin consists of two diastereoisomers, LP-D1 and LP-D2. Being a new cytostatic agent it represents platinum compounds of the third generation and is active in several in vitro tumor models of murine and human origin. To determine the pharmacokinetics of LP-D1 and LP-D2 in cancer patients with and without a normal kidney and liver function, an HPLC procedure was developed and validated. Plasma ultrafiltrate samples were injected into the HPLC system after solid-phase extraction. The standard curves of LP-D1 and LP-D2 in plasma ultrafiltrate were linear over the range 0.071-9.100 and 0.067-8.639 microM, respectively. The recovery from plasma ultrafiltrate was 84% for both diastereoisomers. The within-day accuracy ranged from 98.1 to 100.3% for LP-D1 and from 96.5 to 106% for LP-D2. The between-day accuracy ranged from 99.2 to 101.5% fro LP-D1 and 97.7 to and < or = 6.5% for LP-D2, respectively. For pharmacokinetic purposes the method proved to be sufficiently sensitive, specific and accurate for analysing clinical samples.
Welink
J
J
Department of Medical Oncology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, Netherlands.
Pechstein
B
B
van der Vijgh
W J
WJ
D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003503:Cyclobutanes / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008099:Liver / Q000503:physiopathology*; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009944:Organoplatinum Compounds / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014462:Ultrafiltration
D000970:Antineoplastic Agents; D003503:Cyclobutanes; D009944:Organoplatinum Compounds; C066228:lobaplatin