Journal Article

Stability Study of Fluoxetine in Formalin-Fixed Liver Tissue

Suma Ramagiri, S.K. Shukla and P.K. Sai Prakash

in Journal of Analytical Toxicology

Volume 30, issue 9, pages 692-696
Published in print November 2006 | ISSN: 0146-4760
Published online November 2006 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/30.9.692
Stability Study of Fluoxetine in Formalin-Fixed Liver Tissue

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In the present work, we report conversion of fluoxetine (Prozac), a novel anti depressant to N-methyl fluoxetine in formalin fixed liver tissue. Earlier studies indicate that drugs containing secondary amino group will react with formalin to form corresponding N-methyl derivatives. Even though embalming cadavers is common, it may create problems for forensic toxicologists if a case was not previously suspected. In formalin solutions, fluoxetine is methylated producing N-methyl fluoxetine. N-Methyl fluoxetine standard was synthesized by treating fluoxetine in formaldehyde solution. The structure confirmed by 1HNMR and gas chromatography-mass spectrometry in electron impact ionization mode. Randomly chosen rat liver pieces (200–250 mg) were injected with 100 µg of Fluoxetine. The liver pieces were covered with three different concentrations of formalin, 5%, 10%, and 20%, and at three different pHs, 3.0, 7.0, and 9.5. The reaction was studied for a total period of 30 days, and the reaction products were monitored on days 0, 4, 14, and 30 days. The study indicates that the rate of conversion of fluoxetine to its N-methyl derivative increased with increase in the concentration of formalin and pH of the solution. The conversion is rapid at higher pH values. Fluoxetine was totally converted to its N-methyl derivatives after 30 days in 20% formalin at pH 9.5. Therefore, analysis for parent drug or its N-methyl derivative in embalmed tissues may provide data that will reduce the likelihood of false negatives.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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