DETERMINATION OF THE 2 DIASTEREOISOMERS OF LOBAPLATIN (D-19466) IN PLASMA ULTRAFILTRATE OF CANCER-PATIENTS WITH A NORMAL OR AN IMPAIRED KIDNEY OR LIVER-FUNCTION BY HIGHPERFORMANCE 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 gen eration and is active in several in vitro tumor models of murine and h uman origin, To determine the pharmacokinetics of LP-D1 and LP-D2 in c ancer patients with and without a normal kidney and liver function, an HPLC procedure was developed and validated. Plasma ultrafiltrate samp les were injected into the HPLC system after solid-phase extraction. T he standard curves of LP-D1 and LP-D2 in plasma ultrafiltrate were lin ear over the range 0.071-9.100 and 0.067-8.639 mu M, 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% for LP-D1 and 97.7 to 101.2% for LP-D2. The within-day and the between-day precision were less than or equal to 6.0% and less than or equal to 6.1% for LP-D1 and less than or equal to 3.8% and less than or equal to 6.5% for LP-D2, respectively. For pharmacokinetic purposes the method proved to be sufficiently sensitive, specific and accurate for analysing clinical samples.