Sampath A, Reddy A Raghupathi, Yakambaram B, Thirupathi A, Prabhakar M, Reddy P Pratap, Reddy V Prabhakar
Department of Research and Development, Integrated Product Development, Innovation Plaza, Dr. Reddy's Laboratories Ltd., Survey Nos. 42, 45, 46 & 54, Bachupally, Qutubullapur, R.R. Dist-500072, AP, India.
J Pharm Biomed Anal. 2009 Oct 15;50(3):405-12. doi: 10.1016/j.jpba.2009.05.024. Epub 2009 May 30.
Five impurities (related substances) were detected during the impurity profile study of an antihypertensive drug substance, valsartan. A simple gradient high performance liquid chromatographic method (HPLC) and liquid chromatography-mass spectrometry (LC-MS) were used for the detection. Based on the spectral data (IR, NMR and MS) followed by synthesis, these impurities were characterized as (S)-N-(1-carboxy-2-methylprop-1-yl)-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity I); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-(5-phenylthio)pentanoyl-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity II); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-(5-phenyl)pentanoyl-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity III); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-4-pentenoyl-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity IV); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-(5-hydroxy)pentanoyl-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity V).
在抗高血压原料药缬沙坦的杂质概况研究中检测到了五种杂质（有关物质）。采用简单梯度高效液相色谱法（HPLC）和液相色谱 - 质谱联用（LC - MS）进行检测。根据光谱数据（红外光谱、核磁共振光谱和质谱）并通过合成，这些杂质被鉴定为：(S)-N-(1-羧基-2-甲基丙-1-基)-N-[2'-(1H-四氮唑-5-基)-联苯-4-基甲基]胺（杂质I）；(S)-N-(1-羧基-2-甲基丙-1-基)-N-(5-苯硫基)戊酰基-N-[2'-(1H-四氮唑-5-基)-联苯-4-基甲基]胺（杂质II）；(S)-N-(1-羧基-2-甲基丙-1-基)-N-(5-苯基)戊酰基-N-[2'-(1H-四氮唑-5-基)-联苯-4-基甲基]胺（杂质III）；(S)-N-(1-羧基-2-甲基丙-1-基)-N-4-戊烯酰基-N-[2'-(1H-四氮唑-5-基)-联苯-4-基甲基]胺（杂质IV）；(S)-N-(1-羧基-2-甲基丙-1-基)-N-(5-羟基)戊酰基-N-[2'-(1H-四氮唑-5-基)-联苯-4-基甲基]胺（杂质V）。
