ELSEVIER Journal of Chromatography B, 654 (1994) 159-163 JOURNALOF CHROMATOGRAPHYB: BIOMEDICAL APPLICATIONS Short Communication Determination of fenoverine in tissue samples by high- performance liquid chromatography Robert Ratiney, Alain Astier, Patrick Chariot * Department of Toxicology, Hfpital Henri Mondor, 94000 Cr~teil, France (First received August 3rd, 1993; revised manuscript received December 24th, 1993) Abstract Fenoverine is a spasmolytic, non-anticholinergic phenothiazine derivative that inhibits calcium channel currents. We describe a high-performance liquid chromatographic method for the determination of fenoverine in striated muscle, smooth muscle, myocardium, and liver tissue. Reversed-phase liquid chromatography was performed on a 5 p.m Nucleosil C18 column with acetonitrile-0.015 M phosphate buffer (28:72, v/v) as a mobile phase and detection with ultraviolet at 214 nm. The limit of quantitation of fenoverine in tissue samples was 25 ng injected. This method is well suited for the determination of fenoverine in various organs in animal experiments. 1. Introduction Fenoverine, a spasmolytic, non-anticholinergic phenothiazine derivative that inhibits calcium channel currents [1], has been used in various countries [2,3] in the treatment of some gastroin- testinal and gynecological spasmodic disorders [2,4]. Fenoverine has been repeatedly implicated to play a role in the occurrence of rhab- domyolysis; however the mechanism still re- mains to be elucidated [5-10]. Chromatographic determination of fenoverine in plasma has been presented in one report [11] but a method allowing fenoverine analysis in tissue samples is lacking. In this study, we describe a simple * Corresponding author. 0378-4347/94/$07.00 ~ 1994 Elsevier Science B.V. All rights SSD1 0378-4347(94)00016-X HPLC method for determination of fenoverine in tissue samples. This method has been applied in toxicity studies in rat and human samples. 2. Experimental 2.1. Chemicals Acetonitrile for HPLC and potassium dihydro- genphosphate obtained from Merck (Darmstadt, Germany) were used for the HPLC mobile phase. Methanol (Carlo Erba, Milano, Italy) and n-hexane (Labosi, Paris, France) were used for sample preparation. Fenoverine and MD 230141 (used as internal standard) (Fig. 1) were a gift from Delalande (Paris, France). reserved