Chemical characterization of the photodegradation products of midazolam complexes with randomly methylated-β-cyclodextrin by HPLC and LC-MS/MS
Midazolam, a potent anxiolytic drug with sedative properties, is susceptible to degradation by both light and hydrolysis in aqueous solution. When formulated as an intranasal product it was found to be effective in achieving seizure control in epileptic patients. In order to deliver an adeq...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Serbian Chemical Society
2016-01-01
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| Series: | Journal of the Serbian Chemical Society |
| Subjects: | |
| Online Access: | http://www.doiserbia.nb.rs/img/doi/0352-5139/2016/0352-51391600018A.pdf |
| Summary: | Midazolam, a potent anxiolytic drug with sedative properties, is susceptible
to degradation by both light and hydrolysis in aqueous solution. When
formulated as an intranasal product it was found to be effective in achieving
seizure control in epileptic patients. In order to deliver an adequate
therapeutic dose to a patient, a nasal formulation requires the concentration
of midazolam to be higher than its’ aqueous solubility. One way to increase
midazolam solubility to a therapeutic concentration, is complexation with
randomly methylated-β-cyclodextrin. Thus, it is important to determine how
complexation with cyclodextrin affects the rate of degradation and type of
midazolam degradants that are formed. We have found that complexation with
cyclodextrin decreases its photostability. More importantly, the degradation
profile for midazolam is significantly altered when it is complexed with
randomly methylated-β-cyclodextrin, what we partly confirmed in our previous
work.1 By continuing our study we have found that degradation products, not
observed on the photodegradation of uncomplexed midazolam are observed in
significant quantities when it is complexed with randomly
methylated-β-cyclodextrin. The decreased photostability was accompanied by
the appearance of two new degradation products, an intermediate structure and
a dimer. Photoproduct formation followed the same pattern as in the forced
degradation studies, further confirming the presence of an intermediate. The
production of these new photodegradants, characterized with their MS spectra,
as well as proposed degradation mechanism of midazolam is discussed. |
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| ISSN: | 0352-5139 1820-7421 |