Detection and Quantification of Formaldehyde by Derivatization with Pentafluorobenzylhydroxyl Amine in Pharmaceutical Excipients by Static Headspace GC/MS

Although considered pharmacologically inert, pharmaceutical excipients have been shown to interact with active drug substances to affect the safety and efficacy of drug products.1 Therefore, there is an increasing awareness of the necessity to understanding interactions between excipients and the active pharmaceutical ingredient (API) in finished dosage forms. One of the areas of major concern is the potential chemical interaction between impurities in the excipient with the drug molecules, leading to formation of reaction products.2 Even trace amounts of reactive impurities can cause significant drug stability problems as the quantity of excipients in a formulation often far exceeds that of an API on a weight and molar basis. Trace amounts of reaction products can then easily exceed 0.2% qualification thresholds for a degradation in many drug products.1 Formaldehyde present in excipients has been implicated in the degradation of several drug products where it can form adducts with primary and/ or secondary amine groups.2 It has also been reported that formaldehyde can induce cross-linking in gelatin capsules causing an adverse effect on in-vitro dissolution rates of drugs. Because of the extremely high reactivity of aldehydes, a timely evaluation of their presence in excipients during formulation design is essential to avoid unexpected drug stability problems in later stages of product development. Gas Chromatography/ Mass Spectrometry A P P L I C A T I O N N O T E