Stability studies detection methods

Moreover, it is also possible to detect minor degradation products in the sample by XPS and this makes the method also interesting when performing stability studies. For instance, it is possible to detect the final degradation product polyenes in PVC by means of XPS [89,90], which are usually present in very minor concentrations (ppb and below). However, especially for the detection of polyenes, Raman spectroscopy is a very simple and powerful method, and might therefore be the method of choice in such cases. 

Detection methods, in stability studies, 12, 621 Deuterated solvents, for NMR of air-sensitive compounds,... 

Assays for biological activity, where applicable, should be part of the pivotal stability studies. Appropriate physicochemical, biochemical and immunochemical methods for the analysis of the molecular entity and the quantitative detection of degradation products should also be part of the stability program whenever purity and molecular characteristics of the product permit use of these methodologies. 

Zhang et al. [43] developed and validated a stability indicating HPLC method for the determination of lornoxicam in pharmaceutical formulation. The isocratic procedure was performed in Shimadzu ODS (4.6 mm x 15 cm, 5 pm) column maintained at 25 °C. The mobile phase was degassed mixture of sodium acetate (0.05 mol/L, pH 5.8) and methanol (55 45). The flow rate was 1 ml/min and detection at 290 nm. Selectivity, specificity, linearity, precision, accuracy, and robustness were evaluated to validate the analytical method. Forced degradation studies were performed to provide an indication of the stability-indicating capacity. The stability indicating method for lornoxicam in the injectable dosage was developed and validated. The method can be considered for routine analysis and quality control of lornoxicam in injectable formulation. 

Quantitative determination of a single drug substance in a nonchromo-phoric solvent such as an aqueous or alcohol solution may be a good application for the UV method. In a preformulation study, solubility, dissolution rate, and some stability studies (when degradation products have a different absorption maximum from the parent compound) are performed with the UV technique. UV is extensively used for HPLC detection. 

The stability study was verified over 12 months at -20°C, -i-20°C and +40°C, monitoring the contents of matrix elements (C, H, P, N), minor elements (Na, Cl, Fe, Mn) and trace elements (Hg, Cd, Pb, Se). Measurement methods were INAA, catharometry after combustion in He/02 followed by conversion over Cu/CuO and pressurised digestion followed by ETAAS, CVAAS or ICP-AES. No instability was detected for any of the elements tested, even at prolonged storage at -t-40 C. 

Determining the stability of pharmaceutical products is of importance, and the conventional method at present is to use elevated temperature DSC. Samples are studied at elevated temperatures, typically 70 to 90°C, because it would be impractical, in most cases, to wait the several years it may require for the products of any reaction to build up to detectable levels. In this case, data are recorded at higher temperatures, and the Arrhenius equation is employed to calculate the rate at any desired (usually lower) temperature (45). Of course, any extrapolation requires the assumption that the mechanism of the reaction does not change over the temperature range of both the experiment and the extrapolation. As HSDSC is, by definition, more sensitive than DSC, stability studies can be conducted at lower temperatures, reducing the potential errors introduced by application of the Arrhenius equation. 

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