Photostability and chiral stability of d-chlorpheniramine maleate (d-CPM, S (+)-form), which is an old but clinically useful antihistamine, were investigated by HPLC with an ovomucoid (OVM) or a β-cyclodextrin (β-CD) derivative immobilized chiral columns. Enantiomers of chlorpheniramine maleate (dl-CPM) were successfully separated by an OVM column with resolution (Rs) 3.2 within 10 min under the reversed-phase mode. A β-CD immobilized column was also useful for the separation of enantiomers. Using validated chiral HPLC methods, photostability and chiral inversion study of d-CPM drug substances, its various formulations (syrups, tablets, injections, and powders) under UV irradiation and heating stress conditions were performed in addition to its quality evaluation. As a result of quality evaluation, large content (1-6%) of the minor enantiomer, l-CPM was detected in both d-CPM drug substances and its formulations. Especially ca. 6% l-CPM, which was the largest among tested formulations, was observed in injections. This may be due to its production process (probably sterilization by heat). In photostability studies, maleic acid (cis-form) in d-CPM was converted to fumaric acid (trans-form) in all formulations including the solid type and aqueous solutions of d-CPM, although chiral inversion was not observed under UV irradiation. On the other hand, under the heating conditions, chiral inversion of d-CPM was observed in all formulations and aqueous solutions of d-CPM with an increase of heating temperature and heating time, in addition to cis-trans rearrangement of maleic acid. An increase of l-CPM (chiral inversion) was also observed in d-CPM syrups, powders and tablets stored at the room temperature for one year, showing d-CPM is relatively easily chiral inverted by heat.
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