Terahertz Fingerprint Identification Of Chiral Drug Lansoprazole

Peptic ulcer is a common disease,occurs mainly in the stomach and duodenum.It is difficult to completely cure and has a potential risk of gastric cancer,which seriously affects people’s work and life.Clinically,proton-pump inhibitor(PPI)is widely used to inhibit gastric acid secretion and effectively prevent the occurrence of ulcer.Lansoprazole is a typical chiral drug with sulfur as the chiral center,it has three different structures of S-lansoprazole,Rlansoprazole and racemic lansoprazole.Compared with S-lansoprazole,R-lansoprazole has more than 5 times the duration and intensity of action in vivo and has a lower drug clearance time Based on these pharmacokinetic advantages,R-lansoprazole underwent further clinical development by Takeda and became a new-generation pump inhibitor,which was first marketed in the United States in 2009 and was well received by the market.According to the characteristics of the use of chiral drugs,many countries have promulgated the corresponding guidelines,for chiral drugs racemate and enantiomer should be carried out pharmacological toxicity test,determine the drug use plan,and strictly control the optical purity of the drug.At present,there are many processes to synthesize lansoprazole with single configuration.In order to prevent unqualified drugs from entering the market,ensure the effect of drugs,and prevent chiral flipping in the process of synthesis of single configuration lansoprazole,the real-time and rapid identification of absolute configuration of lansoprazole is particularly important.In recent years,Terahertz(THz)technology has been widely applied in the field of pharmacy.The high correlation between the overall structure of biomolecules and their spectral properties in THz band is an important microscopic basis for the application of THz technology in drug research.The response of drug molecules to THz wave mainly comes from the collective vibration mode determined by the configuration and conformation of macromolecules,which reflects the overall structural information of molecules.Meanwhile,the photon energy of THz wave is lower than that of various chemical bonds,so THz wave will not cause any damage to drugs.In this paper,Terahertz Time-Domain Spectroscopy(THz-TDS)technology was used to study the spectral characteristics of three lansoprazole chiral drugs and this paper mainly does the following three parts:1.The THz absorption spectra of S-lansoprazole,R-lansoprazole and racemic lansoprazole were measured.The three samples showed different absorption spectra in the band of 0.2-2.2THz,and all have their own characteristic absorption peaks(1.78 THz of S-lansoprazole,2.00 THz of R-lansoprazole,1.50 THz of racemic lansoprazole).At the same time,the absorption spectra of 1:1 mixture of S-lansoprazole and R-lansoprazole samples were measured,and it was found that the absorption spectra of the mixed samples showed obvious absorption peaks at1.78 THz and 2.00 THz.The experimental results laid a foundation for the qualitative identification of the absolute configuration of lansoprazole.2.In order to find the three characteristic absorption peak of molecular motion mechanism and further verify the accuracy of experimental results,we use density functional theory(DFT)calculation.The absorption peak by calculated is consistent with the experimental measurement to the absorption peak,verified the accuracy of experimental results.Through DFT calculation,we obtained the vibration modes of three characteristic absorption peaks respectively,and the results showed that the different positions of absorption peaks were caused by the different vibration modes and the different vibration groups within the molecule.3.Powder X-ray diffraction(PXRD)experiments were carried out on S-lansoprazole,Rlansoprazole and racemic lansoprazole respectively,and the X-ray diffraction spectra of the three samples were obtained.The results showed that the X-ray diffraction peaks of the three samples were also different,indicating that the three samples had obviously different crystal structures,which resulted in the difference of THz absorption peaks of the three samples.