Pharmaceutical Analysis, Department of Organic Chemistry, School of Pharmaceutical and Biochemical Sciences, National University of Rosario and Institute of Chemistry of Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario (S2002LRK), Argentina.
J Pharm Biomed Anal. 2011 Aug 25;56(1):16-22. doi: 10.1016/j.jpba.2011.04.017. Epub 2011 Apr 27.
A photostability study of Valsartan (VAL) is reported. Exposure of the drug to UV-vis radiation (λ > 320 nm) yielded two previously unknown compounds, which were detected by HPLC. Preparative amounts of the new potential degradation products (DP-1 and DP-2) were obtained by submitting VAL bulk drug to extensive photodegradation. The impurities were isolated by preparative normal phase column chromatography. Analytical information from the infrared, nuclear magnetic resonance and mass spectral data of the degradation products revealed their structures as N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-N-isobutylpentanamide (DP-1) and N-(diazirino[1,3-f]phenanthridin-4-ylmethyl)-N-isobutylpentanamide (DP-2). DP-1 arose from decarboxylation of VAL, while DP-2 results from further loss of nitrogen from the tetrazole motif of DP-1, with concomitant cyclization to yield a tetracyclic diazacyclopropene derivative.
本文报道了缬沙坦（VAL）的光稳定性研究。药物暴露于紫外可见辐射（λ>320nm）下生成了两种先前未知的化合物，这两种化合物通过 HPLC 检测到。通过将 VAL 原料药进行广泛的光降解，得到了新的潜在降解产物（DP-1 和 DP-2）的大量制备量。通过制备正相柱色谱法分离出杂质。从降解产物的红外、核磁共振和质谱数据中获得的分析信息表明，它们的结构分别为 N-[2'-(1H-四唑-5-基)-联苯-4-基甲基]-N-异丁基戊酰胺（DP-1）和 N-（二氮杂环庚[1,3-f]菲啶-4-基甲基）-N-异丁基戊酰胺（DP-2）。DP-1 是由 VAL 的脱羧产生的，而 DP-2 是由 DP-1 的四唑部分进一步失去氮，同时环化生成四环二氮杂环丙烯衍生物。
