AYALYST, APRIL 1980. VOL. I13 525 Voltammetric Determination of Chlorpromazine Hydrochloride Saadet Dermi? and hci Biryol Department of Analytical Chemistry, Faculty of Pharmacy, University of Ankara, Ankara, Turkey The electrochemical behaviour of chlorpromazine hydrochloride (CPZ-HCI) in sulphuric acid was investigated voltammetrically using ruthenium electrodes and it was subsequently determined by the same method. From the recorded voltammograms it was concluded that CPZ-HCI can be determined in the concentration range 2 x 10-4-8 x 10-4 M (71-284. 3 pg ml-I). The proposed voltammetric method was applied to the determination of CPZ-HCI in tablets used for neuroleptic purposes in Turkey; the amount of effective compound was found to be within the ranges given for a pharmacopoeial procedure.Keywords 1 Chlorpromazine hydrochloride; ruthenium electrode; voltammetry In chlorpromazine hydrochloride (CPZ-HCI) [2-chloro-10-(3- d i me thy 1 amino prop y I) p hen o t hi azi n e mono h y d r oc h 1 o ride ] t h e d i ni e t h y 1 anii n o p r o p y l group h as i rn po r t an t t r a n q u i 11 is i ng effects. C h 1 or pr o m azi n e h y d roc h 1 o ri de can be determined by v ari - ous techniques including chromatographic1.2 gravimetric,'-5 tit r i m e t r i c , {vt-t; spec t r o p ho t om e t ric'). 1 0 and e 1 ect roc he m ical 1 I - I 1 methods. For the pharmacopoeial determination of CPZ-HCI a non-aqueous titrati0nl-~-l7 method is recommended. Typically. i n electrochemical studies, the polarographic behaviour of chlorpromazine has been investigated after chemical oxidation.18 Investigations carried out using solid electrodes were limited by the lack of reproducibilty of results caused by variations in the electrode surface due to surface reactions occurring in the metal itself. For solid electrodes pre-treatment of the electrode is very importantly and once a suitable pre-treatment procedure is used highly reproducible results can be obtained. This paper describes an investigation into the electroana- Iytical behaviour of CPZ-HC1 using ruthenium electrodes subjected to various pre-treatments and discusses the experimental results obtained under optimum conditions. A further aim of this study was to compare the results obtained by applying the proposed technique to the analysis of dosage forms of tablets containing CPZ-HCI.available in Turkey, \vith those of the pharmacopoeia1 technique. Experimental Apparatus The apparatus and the electrode used in the voltammetric determinations were a three-electrode Tacussel PRG-3 system and a ruthenium wire of 1.0 mm diameter (Engelhard). The reference electrode was a Tacussel Type C-10 saturated calomel electrode and a platinum wire (Johnson Matthey) electrode was used as the counter electrode. All electrochemical experiments and electrode pre-treat- ments were performed in a three-compartment experimental cell made of Pyrex glass. Chemicals The chlorpromazine hydrochloride used as a standard was obtained from Eczacibay Pharmaceuticals (Turkey) and the Largactil tablets containing CPZ-HCI (25-100-mg dosage) were obtained from local drugstores.To prepare a 10-3 M stock solution of the standard, CPZ-HCI was weighed and dissolved in 0.2 M HZS04 (as supporting electrolyte). Solutions of different concentrations, for which voltammograms were recorded, were prepared by dilution of this stock solution. Doubly distilled water was used in the preparation of all solutions and spectroscopic determinations were performed using a Pye-Unicam SP 8-100 spectrophotometer. Electrode Pre-treatment The electrodes were pre-treated in order to obtain reprodu- cible results. A potential of -20 mV was maintained between the electrodes in 0.5 M I12SOI for 5 min by bubbling nitrogen through the electrolyte. The electrodes were then washed with doubly distilled water after the circuit had been disconnected and an electrode potential of +400 mV was applied for 15 min.Such a pre-treated electrode is referred to as a non-oxidised electrode. Kecording of Voltammograms The voltammograms were recorded of CPZ-HCI solutions of different concentrations in 0.2 M H2S04 as supporting electrolyte. The experiments were carried out in a cell isolated from the light after each solution had been de-oxygenated by bubbling with nitrogen for 10 min. Throughout the experiment nitrogen was bubbled through the solution, which was stirred continu- ously by a magnetic stirrer. The current - potential graphs were recorded in the potential range +400 to +1500 mV at a scan rate of 0.01 V s-1. (All potentials are versiis a standard hydrogen electrode.) Analysis of pharmaceutical dosage forms Largactil, a commercial drug containing CPZ-HCI, was analysed under the electro-oxidation conditions used for the determination of standard CPZ-HC1.Comparison of the voltammograms obtained for the same concentration of CPZ-HCI in both the standard and drug solutions showed that the additives present in the drug did not affect the procedure. For the drug analysis, 20 tablets were weighed accurately and ground to a fine powder. Largactil tablets containing the equivalent of 100 mg of CPZ-HC1 were weighed accurately, dissolved in 0.2 M H2S04 and made up to 100 ml in a calibrated flask with the same solution. A 20-ml aliquot of the solution was stirred for 1 h with a magnetic stirrer, transferred to a tube and centrifuged. The clear solution (10 ml) at the top of the tube was then removed and made up to 100 ml in a calibrated flask with 0.2 M HZS04.Voltammograms of this solution were recorded under standard working conditions. Results and Discussion Investigation showed that 0.2 M H2S04 was the most suitable supporting electrolyte and that 0.01 mV s-1 was the optimum scan rate. Fig. 1 shows the oxidation graph of 0.2 M H2S04 in the potential range +400 to +1500 mV obtained by linear526 ANALYST, APRIL 1989, VOL. 114 800 600 N I k $400 200 I P i 500 600 700 800 900 1000 11 00 1200 1300 1400 EHlmV Fig. 1. Voltammograms obtained for 0.2 M H,S04 containing various concentrations of chlorpromazine. A non-oxidised electrode was used in stirred solutions. Scan rate, 10 mV s-1. +, 0.2 M H,S04. [Chlorpromazine hydrochloride]: A .10-4; 0 , 2 x 10-4; 0 , 3 x 10-4; x , 4 x 10-4; M, S x I O F ; A, 6.5 x 10-4; 0 , 7 x 10-4; and 0, 8 x lo-.‘ hf Table 1. Results of the analysis of Largactil tablets for chlorpromazine hydrochloride. Calculated Student’s t-value, 1.66; p < 0.05 Found by Found by spectrophotometric voltammetric Sample No. methodlmg per tablet methodimg per tablet 1 2 3 4 5 6 7 8 9 10 100.7 101.2 100.5 101.6 101.4 102. I 100.6 100.5 101.4 102.7 102.4 102.4 100.9 100.9 100.9 99.3 100.9 09.3 97.6 99.3 Mean value . . . . 101.27 +- 0.52 100.39 2 1.08 Standard deviation . . 0.73 1 .so Standarderror . . 0.23 0.47 Theoretical value . . 100 100 scanning before the anodic polarisation of CPZ-HC1 with an unoxidised ruthenium electrode. Although not very distinctive, two steps occur on the graph, at +500 and +900 mV, corresponding to oxidation of the ruthenium electrode surface.The sharp increase at + 1350 to +1300 mV is due to the formation of Ru04 and the evolution of oxygen. The voltammograms of 10-4-10-3 M CPZ-HCI in 0.2 M HzS04 show a distinctive increase in the current and a limiting current corresponding to this step is apparent on most of the graphs from +900 to +1200 mV. The limiting current density at 1000 mV obtained from the voltammogram for the 0.2 M H2S04 supporting electrolyte was subtracted from the corresponding current densities for the graphs shown in Fig. 1. For 2 X 10-4, 3 X 10-4, 4 X 10-4, 5 X 10-4, 6.5 X 10-4, 7 X 10-4 and 8 X 10-4 M solutions of CPZ-HCl the limiting current densities were 115, 150, 184, 215, 275, 295 and 315 PA cm-2, respectively.The calibration graph had the following charac- teristics: correlation coefficient, 0.998; slope, 3.45 x 105; y-intercept, 46.3; and regression standard deviation, 11.8. The linear relationship obtained between concentration and current density showed that the reaction took place by diffusion-controlled processes and it was concluded that CPZ-HCI could be determined quantitatively in a concentra- tion range of 2 x 10-4-8 x 10-4 M. The test solution was exposed to UV light for 30 min and a marked decrease in the current (about 26%) was observed on the voltammograms recorded at the end of this period. Hence the voltammetric method is selective in the presence of the decomposition products. For the quantitative analysis of Largactil tablets by a pharmacopoeia1 technique, the spectrophotometric determi- nation described in reference 20 was employed.The results of the analysis for CPZ-HCl in the tablets obtained by both voltammetric and spectroscopic methods are given in Table 1. The BP states that CPZ-HCl should be in the range 92.5-107.5% .20 The voltammetric and spectrophotometric analysis data obtained in this study fall within this range and, in addition, there is no significant difference between the two techniques. The authors thank the Research Fund of Ankara University and Eczacibay Tlaq Sanayii ve Ticaret A. $. , Turkey, for their financial support. 1 . 2. 3. 4. 5 . 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. References Gonnet, C., and Rocca, J . L . , J .Chromarogr., 1976, 126. 319. Laitem, L., Bello, I . , and Gaspar, P., 1. Chrornatogr., 1978, 156, 327. Blaiek, J . , and Stcjskal, Z., Cesh. Farm., 1955, 4, 246; Anal. AbJtr.. 1956, 3, 530. Blaiek, J . , Phurmazie, 1967, 22, 120. Blaiek, J . . Spinkova, V., and Stejskal, E., An. Farm. Hosp., 1967, 10, 7. Zivanov-Stakic, D.. and Djceric. L.,Arh. Farm., 1977,27,223. Walash, M. I., Rizk, M., Abou-Ouf, A.-M., and Belal, F., Analyst, 1983, 108, 626. Zakhari, N. A., Rizk. M., Walash, M. 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Stationery Office, Lon- don, 1980, p.748. bul, 1974, pp. 159-160. Paper 8101375F Received April 7th, I988 Accepted November 7th, 1988