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A simple, stability-indicating micellar electrokinetic chromatography (MEKC) method was developed and validated for the analysis of mianserin hydrochloride in coated tablets. The method employed (hydroxymethyl)aminomethane (TRIS) 50 mM to which sodium dodecyl sulfate (SDS) 50 mM was added at pH 10.6 as the electrolyte and the voltage applied was 25 kV. The capillary used was 48.5 cm long (40.0 cm effective length and 50.0 µm i.d.) and the detection wavelength was 220 nm. Tetracycline was used as internal standard. The method was validated in accordance with the International Conference on Harmonization (ICH) requirements, which involved specificity, linearity, precision, accuracy and robustness. The stability-indicating capability of the method was established by enforced degradation studies combined with peak purity assessment using photodiode array detection. The degradation products formed under photolytic and oxidative conditions were investigated by electrospray ionization mass spectrometry. The method was linear over the concentration range of 50-130 µg/mL. The method was precise as demonstrated by an inter-day and intra-day relative standard deviation of less than 2.0%. The proposed validated MEKC method showed recoveries between 98.16 and 102.80% of the nominal contents. The Plackett-Burman design was applied for the robustness test in order to examine potential sources of variability by screening a large number of factors in a relatively small number of experiments.Key words capillary electrophoresis; mianserin hydrochloride; mass spectrometry Mianserin hydrochloride (Fig. 1) is a drug for the treatment of depressive illness and depression associated with anxiety. Its antidepressant effect is mainly attributed to presynaptic alfa2-adrenoreceptor blocking activity and to serotonin receptor antagonism. Mianserin is classified as an atypical antidepressant, based on its undefined action mechanism. 1)This drug is considered a weak base with two pK a values (2.7, 8.26) and chemically known as (RS)-2-methyl-1,2,3,4,10,14b-hexahydrodibenzo[c, f ] pyrazino[1,2-α] azepine hydrochloride. In humans, its major metabolic pathways include 8-hydroxylation, N-demethylation, and N-oxidation catalyzed mainly by CYP2D6, and by CYP3A4 and 1A2.2) In rats, the additional metabolite, 8-hydroxy-N-desmethylmianserin is formed from 8-hydroxyminaserin and/or N-desmethylmianserin. 3)From the analytical point of view, methods for its determination in biological fluids [4][5][6] and dosage form 7) have been reported. However, none of the reported methods for the determination of mianserin hydrochloride was shown to be a stability-indicating. It was therefore important to develop and validate a capillary electrophoresis stability-indicating method for this major compound, that can be employed in stability studies and routine quality control of its preparations. In the literature were found three relevant publications on the determination of mianserin enantiomers by capillary electrophoresis (CE). [8][9][10] The use of CE in the pharm...

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant, used in the management of spasticity. This drug is commercially available only as tablets, which highlights the need to develop oral liquid formulations. In the hospital environment, this aspect is circumvented by the preparation of suspensions, to allow administration to children and adults with impaired swallowing, but there are no data regarding their stability. The purpose of this study was to evaluate the physicochemical andmicrobiological stability of liquid dosage forms prepared in the hospital environment from tizanidine hydrochloride tablets, applying high performance liquid chromatography (HPLC) and microbiological analysis. A simple and stability-indicating HPLC method was developed and validated for specificity, linearity, limits of detection and quantification, precision, accuracy and robustness. The liquid formulations were placed in amber PET and glass bottles, which were stored under three different conditions: at room temperature, under refrigeration and at 40 ºC. The liquid formulations were analyzed and demonstrated chemical stability for 56 days, allowing their use for long periods. However, the determination of microbiological stability showed that these formulations are prone to microbial contamination, which has dramatically reduced its stability to 7 days, in both bottles and at all evaluated temperatures.

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