HPLC stability-indicating method drugs

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. 

Since its creation around 1973, modern high-pressure liquid chromatography (HPLC) has played a dominant role in the analysis of pharmaceuticals. It is used in many different applications for example, in content uniformity assays and stability-indicating methods, for the purity profiles of drug substances, or in the analysis of drug metabolism in animals and humans. The heart of all of these assays is the HPLC column. In this chapter, we will describe the fundamental properties of HPLC columns as well as how these properties influence column performance and separation characteristics in pharmaceutical assays. 

Even if HPLC is chosen as the main stability indicating method, CE will be useful as orthogonal technique, especially in cases where the reason of mass balance deviations is unclear. In addition, due to its increased peak capacity and selectivity in comparison to HPLC, the detection of possible enantiomers, stereoisomers, and position isomers, having the same molecular weight and equal/similar spectra as the drug substance may be separated by a secondary CE method. 

G.B. Chaudhari, N. Patel, P.B. Shah, Stability indicating RP-HPLC method for simultaneous determination of atorvastatin and amlodipine from their combination drug products, Chem. Pharm. Bull. 55 (2007) 241-246. 

T. Kubala, B. Gamblhir, and J. I. Borst, A specific stability indicating HPLC method to determine diclofenac in raw materials and pharmaceutical solid dosage forms, Drug Dev. Ind. Pharm, 19 749(1993). 

Xu, Q.A. and Trissel, L.A. Stability-Indicating HPLC Methods for Drug Analysis. Pharmaceutical Press London, 1999. 

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. 

Therefore, admixture studies are performed on parenteral drugs with commonly used intravenous diluents. Studies are performed by preparing admixtures of the drug product with various diluents in an appropriate type of flexible intravenous bag. Initial samples are taken for analysis before the bags are stored in temperature-controlled stability chambers. Subsequent samples may be pulled at 6-, 12-, 24-, 48-, and 72-h time points. The analytical tests commonly performed include visual appearance, pH, and HPLC assay. Degradation products are not commonly tested unless the method has been previously evaluated for specificity and stability-indicating ability with a particular intravenous diluent. This is necessary because there may be differences in the stability profile of the product in its original formulation compared to the admixture solution. Formation of any particulate matter is detected by visual... 

Table 2 contains an example of validation target acceptance criteria for a stability-indicating HPLC method for the assay of an active drug substance and its related compounds. These criteria or others cited in the literature 22>23 can be used as a general guideline when considering acceptance criteria for a validation protocol. 

Xu Q, Trissel L (2003) Stability-indicating HPLC methods for drug analysis. Pharmaceutical Press, London. 

Burana-Osot J, Ungboriboonpisal S, Siiphong L (2006) A stability-indicating HPLC method for medroxyprogesterone acetate in bulk drug and injection formulation. J Pharm Biomed Anal 40 1068-1072. 

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