The use of differential scanning calorimetry for the purity verification of pharmaceutical reference standards.

Reference standards are routinely used in pharmaceutical industry to determine strength, content, and the quality of drug products, active pharmaceutical ingredients (API), preservatives, antioxidants and excipients. Traditionally, chromatographic techniques such as High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC) in conjunction with other analytical techniques have been used to determine the purity and strength of a specific lot of a compound for the purpose of qualifying the lot to use as a reference standard. The assigned purity of the reference standard for a wide variety of compounds can be verified using an absolute method such as Differential Scanning Calorimetry (DSC). In this paper, purity of 16 reference standards was determined by DSC and the results were then compared to the purity values that were obtained using HPLC and other analytical techniques. The results indicate that the purity obtained from DSC analysis is comparable to the chromatographic purity for organic compounds that are at least 98% pure. Use of DSC for purity determination is not appropriate if a compound lacks sharp melting point, decomposes in the defined temperature range or exhibits other thermal event(s) which interfere with the melting point of the compound. The use of DSC as an alternative and or complementary method to verify the purity of a compound as part of the pharmaceutical reference standard certification process is discussed.