HPLC/DAD Assay of Related Impurity Ethyl-4-oxopiperidine-1-carboxylate in Loratadine Through Derivatization with 2,4-Dinitrophenylhydrazine

Assay of ethyl-4-oxopiperidine-1-carboxylate (Impurity H) as related impurity in loratadine (active ingredient or in its pharmaceutical formulations) has been achieved through precolumn derivatization with 2,4-dinitrophenylhydrazine followed by HPLC/DAD. The derivatization reaction was found to be selective, fast, quantitative, and allows good sensitivity when monitored at 368 nm detection wavelength (absolute limit of quantitation is placed around 0.1 µg/mL, meaning 0.01% with respect to the amount of loratadine used in the test solution and 1/10 from the maximum allowed threshold for impurity H). Derivatization conditions and kinetics of the reaction are discussed. For convenience, the HPLC method used for separation of the derivatization product is identical to the method described in the European Pharmacopoeia 6.0, loratadine monograph, the test for related substances (other than impurity H). No interferences from the other compendial cited impurities of loratadine and from the derivatization...