Analytica Chimica Acta 535 (2005) 101–108 Determination of thiazinamium, promazine and promethazine in pharmaceutical formulations using a CZE method Francisco J. Lara, Ana M. Garc´ ıa-Campa˜ na ∗ , Ferm´ ın Al´ es-Barrero, Juan M. Bosque-Sendra Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avd. Fuente Nueva s/n, E-18071 Granada, Spain Received 26 July 2004; received in revised form 30 November 2004; accepted 30 November 2004 Available online 15 January 2005 Abstract We present the validation of a developed method using capillary zone electrophoresis (CZE) for quantitative analysis of three phenoth- iazines: thiazinamium methylsulphate (TMS), promazine hydrochloride (PMH) and promethazine hydrochloride (PTH) in pharmaceutical formulations. The influence of various parameters affecting the CZE separation (buffer pH and concentration, acetonitrile percentage, capil- lary temperature and applied voltage) was investigated by means of multivariate optimization using experimental designs so as to obtain the highest efficiency. The method allows the separation of the phenothiazines in 5.0 min at optimized conditions: 100 mM tris(hydroxymethyl)- aminomethane (Tris) buffer at a pH 8.0, 15% acetonitrile, capillary with 58.5 cm in length at 25 ◦ C and a voltage of 30 kV. Detection occurred at 254 nm. Acceptable precision (relative standard deviation (R.S.D.) 5.3%) and linearity were achieved using the internal standard (IS) method. The limits of detection (LODs) were 2.8 g ml -1 for TMS and 3.3 g ml -1 for PMH and PTH. The method has been successfully applied in the analysis of pharmaceutical formulations. © 2004 Elsevier B.V. All rights reserved. Keywords: Capillary zone electrophoresis; Thiazinamium methylsulphate; Promazine; Promethazine; Pharmaceutical analysis 1. Introduction Capillary electrophoresis (CE) is a complementary ana- lytical technique to high performance liquid chromatogra- phy (HPLC). It presents, as main advantages, low reagent and sample consumption, high separation efficiency and re- duced analysis time. Despite these advantages, CE remains less used in industrial routine analysis; it might be due to the relative limited number of validated quantitative analytical methods in CE [1–3]. Phenothiazines are a group of basic drugs including a phenothiazine ring with different substituents attached at the 2- and 10-position, which are used as antipsychotics, neuroleptics and antihistamines [4]. The 10-substituent is an ∗ Corresponding author. Tel.: +34 958 248594; fax: +34 958 249510. E-mail address: amgarcia@ugr.es (A.M. Garc´ ıa-Campa˜ na). alkyl piperazine group, a piperidine moiety, or an aliphatic side chain containing an amino group. Thiazinamium methylsulphate (TMS) (10-[2-trimethyla- mmonium-propyl]-phenothiazine-methylsulphate), has anti- histaminic and anticholinergic properties. It is administered by intramuscular injection to patients suffering from chronic respiratory diseases. Few methods were developed for the determination of TMS, based on amperometric detection [5], spectrophotometric detection [6], fluorescence quench- ing [7], gas chromatography [8] or thin layer chromatography [9]. More recently, a validated method was established using reverse phase HPLC with UV detection for pharmaceutical quality control [10]. Promazine hydrochloride (PMH) (10- [3-dimethylamino-propyl]-phenothiazine), is a neuroleptic agent with strong anticholinergic, hypotensive and sedative effects. It is used mainly as an antipsychotic and antiemetic agent and additionally as an adjunct agent in the management of severe pain. It is administered in solutions for intramus- 0003-2670/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2004.11.081