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In vivo metabolism of 2-[1′-phenyl-3′-(3-chlorophenyl)-2′-propenylyden]hydraz ino-3-methyl-4(3H)-quinazolinone in rats

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The aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1′-phenyl-3′-(3-chlorophenyl)-2′-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone as a substrate, and as a model compound in rats. The substrate was dissolved in DMSO/water (1∶4) and administered intraperitoneally at a dose of 100 mg/kg in a volume of approximately 0.1 mL. Blood samples were taken before and 30 min, 1.5, 3, 6, 9, 11, 30 and 48 h after i.p. drug administration. The chromatographic separation of the substrate and its metabolites was performed using a stainless steel Novopak C18 column (150 × 4.6 mm i.d., 5-μm particle size). The optimal composition of the mobile phase was reached by introducing different mixtures of pure acetonitrile and water in a linear gradient system. Following the biotransformation of this compound, 2-hydrazino-3-methyl-4(3H)-quinazolinone (M1) and 3-(3-chlorophenyl)-1-phenylprop-2-en-1-one (M2) derivatives were identified together with substrate by comparing them to reference standards using HPLC-UV/DAD. In addition, the composition of these metabolites and substrate was confirmed by LC-MS in plasma.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir, Turkey

    Yasemın Aktan & Kevser Erol

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey

    Sıbel Süzen

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Nesrın Gökhan

  4. Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Semra Koyunoĝlu & Akgül Yeşjxada

  5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, 34668, Haydarpasa, İstanbul, Turkey

    Bedıa Koçyıĝıt Kaymakçioĝlu & Sevım Rollas

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  1. Bedıa Koçyıĝıt Kaymakçioĝlu
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  2. Yasemın Aktan
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  5. Semra Koyunoĝlu
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  7. Akgül Yeşjxada
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  8. Sevım Rollas
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Kaymakçioĝlu, B.K., Aktan, Y., Süzen, S. et al. In vivo metabolism of 2-[1′-phenyl-3′-(3-chlorophenyl)-2′-propenylyden]hydraz ino-3-methyl-4(3H)-quinazolinone in rats. European Journal of Drug Metabolism and Pharmacokinetics 30, 255–260 (2005). https://doi.org/10.1007/BF03190629

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  • DOI: https://doi.org/10.1007/BF03190629

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