富马酸替诺福韦二吡呋酯的质谱分析及NMR测定富马酸相对含量

目的: 利用电子轰击(EI)质谱进行分析,得到富马酸替诺福韦二吡呋酯(TDF)的质谱特征;建立核磁共振氢谱(¹H-NMR)的方法分析富马酸与替诺福韦二吡呋酯的结合比例。 方法: 采用EI质谱对富马酸替诺福韦二吡呋酯进行分析,对质谱主要碎片峰进行归属;在对药物进行结构分析的基础上利用¹H-NMR信号强度与质子数成正比的特点,对化合物中富马酸的相对含量进行定量分析。 结果: EI质谱特征证明所检测化合物所结合的有机酸为富马酸,高分辨质谱检测得到的精确质量数和元素组成结果与替诺福韦二吡呋酯的分子式相符,主要质谱碎片峰归属得到合理解释。从¹H-NMR特征定量峰可以计算出富马酸与替诺福韦二吡呋酯结合比例。 结论: 本方法测定结果准确,为富马酸替诺福韦二吡呋酯的生产和鉴定提供可靠的数据。

Objective: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor which is comprised of adenine derivative and fumarate at the ratio of 1:1.It was also reported that the combination ratio of tenofovir disoproxil (TD) and fumarate (FA) could be 2:1 under different solvent or crystallization rate.In present study,electron impact (EI) mass spectrometry character of TDF was obtained,and ¹H-NMR method was established to determine the combination ratio of TD/FA. Method: EI mass spectrometry was used to analyze the mass character of TDF,and the major fragments were illustrated.¹H-NMR spectrometry was applied to determine the combination ratio of TD/FA basing on the principle that the ¹H-NMR signal strength was proportional to proton numbers. Results: From the EI mass character,fumarate could be confirmed.The results of accurate mass and the element composition of the samples were consistent with those of TDF.Major fragments could be illustrated.The combination ratio of TD/FA could be successfully calculated from the selected peaks of ¹H-NMR. Conclusion: The results of the method are accurate,which provide a comprehensive reference for production and identification of TDF.

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