Iida Motoo, Kikura-Hanajiri Ruri
Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences.
Yakugaku Zasshi. 2021;141(8):1041-1048. doi: 10.1248/yakushi.21-00090.
Some controlled substances, such as stimulants and narcotics, have asymmetric carbons in their molecules. Because the enantiomers do not always show the same pharmacological effects, and there are substances with different controls due to differences in their stereochemistry, a simple and unambiguous method for assessment of the composition of enantiomers is necessary. In this study, to develop a simple and rapid stereoscopic identification method for methamphetamine and its raw materials (ephedrine and pseudoephedrine), the H-NMR method was studied using three commercially available chiral solvating agents (CSAs); 1,1'-bi(2-naphthol)(BINOL), 2,2,2-trifluoro-1-(9-anthryl)ethanol (TFAE) and α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA). In addition, the accuracy of the optical purity, which was measured using samples mixed with enantiomers in various ratios, was investigated. The NMR peaks of the enantiomers were separated by adding (R)- or (S)-form of BINOL, TFAE or MTPA to the chloroform-d solution of methamphetamine, ephedrine or pseudoephedrine. A sufficient discrimination of enantiomers was obtained by adding about 10 equal amounts of each CSA to the solutions. With regard to the optical purity, it was possible to determine accurately the mixing of small amounts of enantiomers of about 5% even if the NMR peaks did not reach the baseline separation, when impurity peaks do not overlap. This method will be one of the useful techniques for the rapid and simple discrimination of enantiomers of illegal methamphetamine and its raw materials.
一些管制物质，如兴奋剂和麻醉药品，其分子中含有不对称碳原子。由于对映体并不总是表现出相同的药理作用，并且由于其立体化学的差异存在不同管制的物质，因此需要一种简单明确的方法来评估对映体的组成。在本研究中，为了开发一种用于甲基苯丙胺及其原料（麻黄碱和伪麻黄碱）的简单快速的立体鉴定方法，使用三种市售手性溶剂化剂（CSA）研究了氢核磁共振（H-NMR）方法；1,1'-联（2-萘酚）（BINOL）、2,2,2-三氟-1-（9-蒽基）乙醇（TFAE）和α-甲氧基-α-（三氟甲基）苯乙酸（MTPA）。此外，还研究了使用以各种比例混合对映体的样品所测得的光学纯度的准确性。通过向甲基苯丙胺、麻黄碱或伪麻黄碱的氘代氯仿溶液中加入（R）-或（S）-形式的BINOL、TFAE或MTPA，对映体的核磁共振峰得以分离。向溶液中加入约10等量的每种CSA，可获得对映体的充分区分。关于光学纯度，即使核磁共振峰未达到基线分离，当杂质峰不重叠时，也能够准确测定约5%的少量对映体的混合情况。该方法将成为快速简单鉴别非法甲基苯丙胺及其原料对映体的有用技术之一。
