A high-performance liquid chromatography-diode array detection method was developed and validated to simultaneously determine tramadol (TMD), metamizole (MTZ), ropivacaine (RPV), and bupivacaine (BPV) in the presence of 4-methylaminoantypirine (4-MAA), the metabolite of MTZ, in analgesic mixtures samples used in Patient Controlled Analgesia (PCA). Chromatographic separation is achieved with a C-18 column using a mixture of ACN-methanol-water adjusted to pH 3.0 with NaH(2)PO(4) 0.05M (10:25:65 v/v) in an isocratic mobile phase at a flow rate of 0.8 mL/min. 0.5 mg/mL of Na(2)SO(3) in the water of the mobile phase was necessary to prevent the fast MTZ hydrolysis process to 4-MAA. Ultraviolet-diode array detection was used and chromatograms were registered at the wavelength of 230 nm. The method was linear in the range of 2.2-80.0 mg/L for TMD, 4.1-140.0 mg/L for MTZ, 2.3-40.0 mg/L for RPV, and 2.9-40.0 mg/L for BPV. Validation of the method was made in terms of accuracy, intra- and interday precision, as well as quantification and detection limits. The hydrolysis of MTZ to 4-MAA was studied and verified by mass spectrometry. The developed method was used successfully to evaluate the chemical stability of binary analgesic TMD mixtures with MTZ, RPV, or BPV. The mixtures were tested at standard concentrations used in PCA and in different storage conditions. When mixtures contained MTZ, a chromatographic peak from the metabolite 4-MAA was always detected in the chromatograms.