Development of an LC–DAD Method for Analysis of Dexketoprofen, Tramadol, and Haloperidol. Study of the Stability of Mixtures Used for Patient-Controlled Analgesia Antonio Salmero ´n-Garcı ´a 1 , Emilio Lopez-Lopez 2 , Eva Roma ´n 1 , Jose ´ Cabeza 1 , Natalia Navas 2 , Luı ´s Fermı ´n Capita ´ n-Vallvey 2,& 1 Hospital Pharmacy, University Hospital San Cecilio, 18012 Granada, Spain 2 Solid-Phase Spectrometry Research Group, Department of Analytical Chemistry, Campus Fuentenueva, Faculty of Sciences, University of Granada, 18071 Granada, Spain; E-Mail: lcapitan@ugr.es Received: 21 January 2008 / Revised: 30 April 2008 / Accepted: 8 July 2008 Online publication: 31 July 2008 Abstract Dexketoprofen (D-KTP), tramadol (TMD), and haloperidol (HLP), two analgesic agents and an adjuvant, respectively, were analysed simultaneously in 0.9% NaCl and 5% glucose by use of a new, rapid LC–DAD method. Chromatographic separation was achieved on a C 18 column with 50:50 (v/v) acetonitrile–sodium dihydrogen phosphate (pH 4.10; 0.1 M) as mobile phase at a flow rate of 1 mL min -1 . Ultraviolet diode-array detection was used. The absorbance of the eluate was monitored at 210 nm. The retention times of the three compounds were 2.0, 4.0, and 8.3 min for TMD, HLP, and D-KTP, respectively; the total run time was 9 min. The method was validated for linearity, accuracy, reproducibility, and limits of quantification and detection. Calibration functions were established between 100.0 and 225.0 mg L -1 for D-KTF, between 200.0 and 450.0 mg L -1 for TMD, and between 2.0 and 4.5 mg L -1 for HLP. Recoveries were >98% with precision less than 2.2% for the three drugs prepared in both 0.9% NaCl and 5% glucose. The method was successfully used to evaluate the chemical stability of this drug mixture at the usual concentration used in patient-controlled analgesia. Samples were prepared at 2.5 mg mL -1 D-KTF, 5.0 mg mL -1 TMD, and 0.05 mg mL -1 HLP in 0.9% NaCl and in 5% glucose. Stability was assumed if the loss was less than 10% of the initial concentration. Five different storage conditions were tested for 30 days and the drug mixture was stable under all these. Stability was independent of medium, 0.9% NaCl or 5% glucose. The best results were obtained for the drug mixture stored at 4 °C in darkness. Keywords Column liquid chromatography Diode-array detection Dexketoprofen, tramadol and haloperidol mixture Patient-controlled analgesia Stability compatibility study Introduction Combinations of different drugs are often used in clinical practice to relieve post-operative pain by patient-con- trolled analgesia (PCA) [1, 2]. Little or no information is available about the chemical stability and compatibility of the analgesic mixtures used. Because these analgesic mixtures are not com- mercially available, when they are needed they must be prepared in the hospital pharmacy. The composition of the mixture used depends on the type of surgery performed. One such drug mix- ture is a combination dexketoprofen (D-KTF), tramadol (TMD), and halo- peridol (HLP). The structures of these drugs are shown in Fig. 1. D-KTF, (S)-2-(3-benzoylphenyl)pro- pionic acid, is a non-opioid, propionic non-steroidal anti-inflammatory drug (NSAID) which has analgesic, anti- inflammatory, and antipyretic properties [3]. It is mainly used to reduce inflamma- tion and relieve pain [4]. TMD, trans-(±) -2-[(dimethylamino)methyl]-1-(3-methoxy phenyl)cyclohexanol, is a synthetic, cen- trally acting analgesic agent. The drug acts as an opiate agonist by selective activity at l-opioid receptors. In addition to opiate agonist activity, TMD inhibits 2008, 68, 767–772 DOI: 10.1365/s10337-008-0751-y 0009-5893/08/11 Ó 2008 Vieweg+Teubner | GWV Fachverlage GmbH Original Chromatographia 2008, 68, November (No. 9/10) 767