UPLC® method development and validation for the assay of the photolabile drug nifedipine and its trace level degradation products.

Abstract

Quality assurance regulations require that pharmaceutical drugs are highly pure. This is in order to ensure the safety and efficacy of medicines for patients, two fundamental issues of importance in treatment. The safety of a drug is determined by both its pharmacological and toxicological profile as well as impurities present in its dosage form. Impurities may have pharmacological and toxicological effects that outweigh any benefit from the dosage form administration. While the use of a drug to treat a patient is a balance of risk and benefit, impurities in pharmaceuticals provide only risk. Therefore, pharmaceutical companies must characterise what molecules may be present and be able to identify them at low levels or as low as reasonably practicable (ALARP). This involves reducing risk to an acceptable level without disproportionate resource expenditure. Molecule characterisation involves the identification, structural elucidation and quantitative determination of impurities and degradation products. Impurity analysis is therefore a very important field in pharmaceutical characterisation as it allows assurance that a drug is safe and of sufficient quality (Görög, 2000). Due to newer analysis methods becoming available and the need to detect impurities at ever lower levels, ongoing method development and transfer of newer techniques to the quality control laboratory is a reasonable regulatory expectation. However pharmaceutical companies can be innately conservative, with a to change and adaptation to new techniques that can require significant resource investment. Although current techniques may appear adequate, when dealing with impurities that can impact patient safety, in particular genotoxic impurities, this resource allocation is prudent.