太赫兹时域光谱技术定性定量分析抗结核药物中的吡嗪酰胺和异烟肼

目的: 利用太赫兹时域光谱(terahertz time-domain spectroscopy,THz-TDS)技术对抗结核类药物中吡嗪酰胺、异烟肼、利福平三者进行光谱采集,获得三者不同的频谱响应和折射率色散关系;建立吡嗪酰胺和异烟肼含量与光谱曲线的定量分析模型,提供一种新的含量快速检测方法。方法: 通过采集时域光谱数据,获得吡嗪酰胺、异烟肼及其混合药物在THz 波段的吸收谱与折射率谱,结合密度泛函理论定性归属吡嗪酰胺和异烟肼的分子振动模式;采用偏最小二乘法(partial least squares,PLS)对混合药物中吡嗪酰胺和异烟肼的含量进行回归拟合分析。结果: 吡嗪酰胺在0.52、0.72 和1.42 THz 处有吸收峰;异烟肼在1.17 和1.42 THz 处有吸收峰;利福平在0.85 THz 处有较弱的特征吸收峰,故3 种抗结核药物可在THz 波段明显识别。混合物中位于0.52、0.72 和1.17 THz 处的特征吸收峰已归属。随着混合物中吡嗪酰胺质量的增加,样品的吸收系数和折射率都呈现线性的关联度。由回归分析可得,基于吸收系数的吡嗪酰胺含量的PLS 模型的相关系数高达0.999 9,均方根误差为0.203 3%,检出极限和定量限分别为0.761 3% 和2.307 1%,最大绝对误差为0.491 0%。结论: THz-TDS 技术具有操作简单、检测快速、结果可靠的优点,可用于吡嗪酰胺与异烟肼的定性定量分析。

Objective: To utilize terahertz time-domain spectroscopy(THz-TDS)technology for the determination and analysis of anti-tuberculosis(anti-TB)drugs such as pyrazinamide,isoniazid and rifampicin,so as to get the spectral response and dispersive relationship of refractive index;to establish a quantitative analysis model between content and THz spectral of pyrazinamide and isoniazid,which may provide a new method for anti-TB drugs content rapid determination. Methods: The refractive index and absorption spectrum of pyrazinamide,isoniazid and its mixture were obtained by terahertz time-domain spectroscopy(THz-TDS);Density functional theory (DFT)calculation was performed to assign the vibrational modes of pyrazinamide and isoniazid. Partial least squares(PLS)regression was adopted to regressively analyze the concentrations of pyrazinamide and isoniazid. Results: Experimental results showed that there were distinctly different absorption features for pyrazinamide at around 0.52,0.72 and 1.42 THz,isoniazid at around 1.17 and 1.42 THz,and rifampicin at 0.85 THz,which indicated that the three anti-TB drugs could be identified and recognized in THz region. Characteristic absorption peak of mixture at 0.52,0.72 and 1.17 THz were also assigned based on the simulation DFT results. Furthermore, absorption coefficient and refractive index of mixtures have considerable relevance with the increasing content of pyrazinamide in mixture. The results showed that there was a good linear relationship between the content of pyrazinamide and isoniazid in the mixture. The correlation factors from PLS model based on absorption coefficient were up to 0.999 9 for pyrazinamide. The root mean square error of PLS model were 0.203 3%;the detection limit of concentration and limit of quantitation in mixture were 0.761 3% and 2.307 1%,while maximum absolute error was 0.491 0%. Conclusion: THz-TDS technique,as a quick and non-damaging measurement,can be applied to the content determination of anti-TB drugs.