Evaluation of electrophoretic method versus chromatographic, potentiometric and absorptiometric methodologies for determing pKa values of quinolones in hydroorganic mixtures

The advantages of using capillary electrophoresis (CE) over other methodologies for determining pK_a values of drugs in hydroorganic media are discussed. The focus of the discussion based upon the pK_a values of a series of quinolones determined in acetonitrile (MeCN)–water mixtures by CE, liquid chromatography, potentiometric, and spectrophotometric methods.     

Validation of a spectrophotometric method for the determination of iron (III) impurities in dosage forms

A spectrophotometric method (λ=535 nm) for the iron (III) impurities determination in iron protein–succinylate complex syrup using thioglycolic acid in basic ambient was proposed and validated. Assay samples were treated with 0.1 N hydrochloric acid and centrifuged to remove the interfering active drug. Linear response (r=0.9999) was observed over the range of 0.005–0.2% of the iron (III) with respect to the complex nominal concentration. The accuracy could be considered very satisfactory (recovery=97–99%). The intra-day precision (RSD) of impurity amongst six independent sample preparations, was 1.4%, and there was no significant difference between intra- and inter-day studies. Intermediate precision indicated that the assay possessed high degrees of ruggedness. The limit of quantitation was 0.005% of impurity with respect to the active drug. The results obtained for iron (III) were compared statistically with those obtained with the standard addition method by means of the Student's t-test and the variance ratio F-test; no significative difference was found.     

Optimisation and validation of a rapid and efficient microemulsion liquid chromatographic (MELC) method for the determination of paracetamol (acetaminophen) content in a suppository formulation

A rapid and efficient oil-in-water microemulsion liquid chromatographic method has been optimised and validated for the analysis of paracetamol in a suppository formulation. Excellent linearity, accuracy, precision and assay results were obtained. Lengthy sample pre-treatment/extraction procedures were eliminated due to the solubilising power of the microemulsion and rapid analysis times were achieved. The method was optimised to achieve rapid analysis time and relatively high peak efficiencies. A standard microemulsion composition of 33 g SDS, 66 g butan-1-ol, 8 g n-octane in 1l of 0.05% TFA modified with acetonitrile has been shown to be suitable for the rapid analysis of paracetamol in highly hydrophobic preparations under isocratic conditions. Validated assay results and overall analysis time of the optimised method was compared to British Pharmacopoeia reference methods. Sample preparation and analysis times for the MELC analysis of paracetamol in a suppository were extremely rapid compared to the reference method and similar assay results were achieved. A gradient MELC method using the same microemulsion has been optimised for the resolution of paracetamol and five of its related substances in approximately 7 min.