Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine
Eva Saar, Dimitri Gerostamoulos, Olaf H Drummer & Jochen Beyer
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abstract
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Olanzapine (OLZ) is amongst the most commonly prescribed
antipsychotic drugs and is associated with substantial instability.
The aim of this study was to investigate the instability of OLZ and
to identify the degradants formed from its breakdown. Three
experiments were conducted to monitor the degradation of OLZ and the
formation of degradants in blood (1), water (2), and post-extraction
at 4 °C (3). All three sample sets were analysed in duplicate
and repeated in the absence (A) and presence (B) of 0.25% ascorbic
acid. One degradant was identified in sample sets 2A and 3A with m/z
329 and confirmed as 2-hydroxymethyl-OLZ (2-OH-OLZ) using LC-MS
techniques. The addition of 0.25% ascorbic acid slowed the
degradation of OLZ down in all three experiments and inhibited the
formation of 2-OH-OLZ in sample sets 2A and 3A. To investigate the
influence of oxygen on the degradation of OLZ and the formation of
2-OH-OLZ in water, an additional experiment (4) was conducted.
Sample sets were prepared containing different vortexing or
sonication steps in order to alter the oxygen content in the
samples. Statistical analysis confirmed that degradation increased
significantly following vortexing for 1 min while sonication did not
affect the rate of degradation of OLZ further suggesting the
involvement of oxygen in the degradative processes. 2-OH-OLZ was
only identified as a degradant of OLZ in aqueous solutions. It also
degrades over time but its product is currently unknown and is under
investigation.
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citation
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Saar E, Gerostamoulos D, Drummer O H, Beyer J. Identification of
2-hydroxymethyl-olanzapine as a novel degradation product of
olanzapine. Forensic Sci Int 2012; 220:74-9.
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type
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journal paper/review (English)
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date of publishing
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23-02-2012
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journal title
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Forensic Sci Int (220/1-3)
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ISSN electronic
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1872-6283
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pages
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74-9
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PubMed
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22365172
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DOI
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10.1016/j.forsciint.2012.01.029
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