The thioxanthene class of drugs is effective in the systematic treatment of psychoses. They are most appropriately used in the therapy of schizophrenia, organic psychoses and other idiopathic psychotic illnesses. 1 However, these drugs have other clinically useful properties, including anti-emetic, antinausea and antihistamine effects, and the ability to potentiate analgesics, sedatives and general anaesthetic actions. 1 Several methods have been reported for the determination of thioxanthenes either in pure form, in dosage forms or in biological fluids. Zuclopenthixol hydrochloride (ZUC) and Flupentixol decanoate (FLU) are official in BP, 2 while Thiothixene (THI) is official in USP only.
3The BP recommends a non-aqueous titration method for evaluating the raw material of ZUC and FLU; for their dosage forms, spectrophotometric methods are described.The USP recommends an HPLC method for the determination of THI in raw material and its dosage forms. Other procedures for the determination of thioxanthenes involving gravimetry, titrimetry, spectroscopy, polarography, fluorometry, chromatography and radioimmunoassay have been reported in the literature. These were reviewed by Belal et al. 4 in 1997. Other reported methods beyond the review include: fluorometry, 5 HPLC 6,7 and voltammetry. 8 Reviewing the literature revealed that up to the present, nothing has been published concerning the CL determination of ZUC, FLU and THI.CL reactions have been widely used for sensitive and selective detection in flow injection and chromatographic analysis. ] reaction has been used for determining some drugs, e.g. mefenamic and flufenamic acids 14 and some fluoroquinolones. 15 The present paper describes the development of a simple flow injection chemiluminometric method for the determination of ZUC, FLU and THI based on the CL reaction of the studied drugs with Ru(dipy)3 2+ and Ce(IV) in a sulfuric acid medium. This method has been satisfactorily applied to the determination of the studied drugs in dosage forms and biological fluids.
Experimental
Apparatus and manifoldThe flow system used for the determination and CL detection of ZUC, FLU and THI is shown schematically in Fig. 1. A Gilson Minipuls 3MP4 peristaltic pump (two channels, variable speed) was used to drive the carrier and the reagent streams through the flow system. Each stream was pumped at a constant flow rate (Table 1) ], chemiluminescence (CL) was developed for the rapid and sensitive determination of three thioxanthene derivatives, namely zuclopenthixol hydrochloride, flupentixol hydrochloride and thiothixene. The method is based on the CL reaction of the studied thioxanthenes with [Ru(dipy)3 2+ ] and Ce(IV) in a sulfuric acid medium. Under the optimum conditions, calibration graphs were obtained over the concentration ranges 0.002 -6 µg/ml for zuclopenthixol hydrochloride, 0.5 -15 µg/ml for flupentixol hydrochloride and 0.05 -7.5 µg/ml for thiothixene. The limits of detection (s/n = 3) were 4.2 × 10 -9 mol/l zuclopenthixol hydrochloride, 2 × 10 -8 mol/l flupe...