HPLC stability-indicating method development

To develop an HPLC stability-indicating method for Type I or II dissolution, the linearity must be wide enough, in combination with good sensitivity and minimal interference, to accommodate concentrations from low (possibly LOQ) to very high end, as the samples drawn represent the cumulative drug amount dissolved over time. As for an FiPLC method that is designed for Type VII dissolution, the linearity should accommodate the lower concentrations since it is a drug measurement of a controlled-release system. 

Hasan et al. [21] developed a reversed-phase HPLC method for the determination of lomoxicam. The method is using acetonitrile phosphate buffer (pH 6) (50 50, v/v) as mobile phase at a flow rate of 1 ml/min and UV detection at 275 nm. This method is suitable as a stability indicating method for the simultaneous determination of lomoxicam in presence of its acid-induced degradates either in bulk powder or in pharmaceutical formulations. 

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. 

To meet the speed and high efficiencies in separations demanded by the pharmaceutical industry, combined HPLC methods have been frequently used to simultaneously determine combination products [67]. A stability-indicating method for the simultaneous determination of aspirin and warfarin in warfarin sodium/aspirin combination tablets has been recently developed and validated [68]. In another example [69], the simultaneous determination of enalapril (2) and its two degradants, enapril-DKP (3) and enalapril-diacid (4), and felodipine (5) and its degradant, named HI52/37 (6) was achieved using combined method approach. 

A selective, sensitive and stability indicating reversed phase-HPLC method was developed for the determination of clarithromycin antibiotic in human plasma. 

A stability indicating HPLC method has been developed to measure etodolac in presence of three main degradants, 7-ethyl-2-( 1 -methylene-propyl)- 1 -//-indole-3 -ethanol, the decarboxylated product of etodolac, and 7-ethyltryptophol [23]. A reverse phase ODS column (15 cm x 0.41 cm i.d., 5 pm particles) was used to achieve separation. The mobile phase... 

In Section 8.2, the aim of analysis is emphasized especially for the API (active pharmaceutical ingredient) and the drug product. The workflows and the rationale at major decision points during synthetic processing steps where HPLC can be applied in process development are elaborated upon. For example, a fast method is needed to monitor reaction conversion of two components. However, a more complex method would be needed for stability-indicating purposes where multiple degradation products, synthetic by-products, and excipient peaks need to be resolved from the active pharmaceutical ingredient. 

The HPLC method development requirements using short columns and fast HPLC to determine the assay concentration for each polymorph at the different temperatures are the same as for solubility determination. However, for stability evaluation of the different polymorphs a stability-indicating HPLC method should be used. 

A reliable analytical method must be available before preformulation studies are started and hence method development activities must precede preformulation activities. The analytical method should be capable of separating the active and any major degradation product(s) and thus be stability-indicating. Analytical methods such as titration and ultraviolet (UV) spectroscopy are not used since they are not considered to be stability-indicating. Only HPLC has been widely used as the method of choice in recent years because of its efficiency, applicability for a wide range of chemical compounds, and ease of... 

In developing HPLC methodology, these validation requirements stipulate that stability-indicating impurity methods be designed and validated to ... 

Ruan J, Tattersall P, Lozano R, Shah P (2006) The role of forced degradation studies in stability indicating HPLC method development. Am Pharm Rev 9 46-53. 

Zhang J, Miller RB, Jacobus R (1997) Development and validation of a stability-indicating HPLC method for the determination of degradation products in dipyridamole injection. Chromatographia 44 247-252. 

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