对乙酰氨基酚的太赫兹时域光谱研究

太赫兹波由于其特有的透视性、安全性及光谱分辨本领高等特点，为太赫兹时域光谱技术(Terahertz time-domain spectroscopy, THz-TDS)在物质检测、物质结构辨别、物质定性及定量分析等方面的应用奠定了基础。药品，作为预防和治疗疾病并规定有适应症或者主治功能的物质，一直跟人们的生活息息相关。但是，近年来药品由于质量问题从而危害人们身体健康的新闻屡见不鲜，迫切需要行之有效的药品检测方法的呼声越来越多。而太赫兹时域光谱技术作为一种新型的无损检测的光谱技术，逐步开始被应用到药品检测中。基于此，采用太赫兹时域光谱技术研究了对乙酰氨基酚的太赫兹特征谱。首先，采用太赫兹时域光谱技术测试了对乙酰氨基酚在0.3～4.5 THz范围的太赫兹光谱，实验获取了六个特征吸收主峰和一个肩峰，分别位于1.46，1.88，2.11，2.52，2.95，3.48和4.27 THz；接着，采用密度泛函理论对光谱进行解析，基于气态理论的计算结果，发现实验吸收峰有分子内作用力的贡献，但由于其未能考虑分子间作用力，无法全面对实验吸收峰进行解析；进一步，采用固态密度泛函理论模拟，经过实验和理论结果对比，发现1.46和2.11 THz的吸收峰既有分子间作用力也有分子内作用力，1.88，2.52和2.95 THz处的吸收峰主要来源于分子间作用力，3.48和4.27 THz处的吸收峰主要来源于分子内作用力；最后，对商用品牌中美史克牌的对乙酰氨基酚片做了变质处理，测试其在变质前后0.3～2.75 THz范围内的太赫兹特征峰，通过比较发现，商用药片与对乙酰氨基酚样品的吸收峰完全匹配，说明可以借助THz特征峰对药品进行标定；通过对比对乙酰氨基酚片变质前后的THz吸收谱，发现变质后的药片原有的THz特征峰基本消失，这一方面说明位于0.3～2.75 TH范围内的THz特征峰1.46和1.88 THz虽有分子内作用的贡献，但是主要源于分子间作用力，另一方面也说明随着药品化学特性变化，其对应的THz指纹吸收峰也会发生改变；变质后的药片产生了位于0.69 THz的新特征吸收峰，说明药片在变质后已经形成新的分子间作用力，药品的化学性质已经发生了变化，产生了新的物化功能。

Terahertz Time-Domain Spectral Study of Paracetamol

Terahertz (THz) has laid a foundation for applying terahertz time-domain spectroscopy (THz TDS) in material detection, structure resolution, qualitative and quantitative analysis due to its unique characteristics of perspective, security and high spectral resolution. As the prevention or treatment of human diseases, drugs have always been closely related to people’s lives. However, recently the news of drugs endangering people’s health is often seen due to their quality problems. There are more and more calls for effective drug detection methods. THz-TDS, as a new non-destructive detection technology, has been gradually applied to drug detection. Thus, in this paper, we studied the THz absorption spectra of paracetamol using THz-TDS. Firstly, the THz spectra of paracetamol were measured in the range of 0.3～4.5 THz. Six characteristic absorption peaks and one shoulder peak were obtained. Specifically, these peaks are located at 1.46, 1.88, 2.11, 2.52, 2.95, 3.48 and 4.27 THz. Then, the simulation calculation based on isolated-molecule density functional theory was carried out. It was found that the intramolecular vibrations contributed to the experimental peaks. However, the -isolated-molecule simulation cannot interpret the measured peaks completely because intermolecular forces are not taken into account. Then the solid-state simulation was performed to interpret the measured peaks. Depending on the comparison between experimental and theoretical results, it was found that the absorption peaks of 1.46 and 2.11 THz are caused by the combination of intermolecular and intramolecular forces, the absorption peaks of 1.88, 2.52 and 2.95 THz mainly come from the intermolecular forces, and the absorption peaks of 3.48 and 4.27 THz primarily originate from the intramolecular forces. Finally, the THz absorption peaks of commercial paracetamol tablets in the range of 0.3～2.75 THz before and after the deterioration were measured. According to the comparison, it was found that the absorption peaks of commercial tablets and paracetamol samples were completely matched, indicating that the drug can be calibrated by the THz characteristic peak. Besides, the THz characteristic peaks in CNR measurement are all disappeared, implying that intermolecular forces mainly contribute the THz peaks of 1.46 and 2.11 THz. On the other hand, it also suggested that the corresponding THz absorption peaks of drugs would be changed with chemical properties. A new characteristic absorption peak at 0.69 THz emerged in the CNR measurement, indicating that the new intermolecular forces have been formed and the new physicochemical functions are produced after deterioration.