Piperazine-based drugs, such as N-benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2-, 3- and 4-pyridylmethylpiperidine (2-PMP, 3-PMP and 4-PMP respectively) were subjected to the hyperpolarisation technique SABRE (Signal Amplification By Reversible Exchange) in order to demonstrate the use of this technique to detect these piperazine-based drugs. Although BZP was not hyperpolarised via SABRE, 2-PMP, 3-PMP and 4-PMP were, with the ortho- and meta-pyridyl protons of 4-PMP showing the largest enhancement of 313-fold and 267-fold respectively in a 1.4 T detection field, following polarisation transfer at earth's magnetic field. In addition to the freebase, 4-PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of three equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4-PMP.3HCl (ca. 20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138-fold enhancement for the ortho-pyridyl protons). The amount of 4-PMP.3HCl present in the simulated tablet was quantified via NMR using D2 O as a solvent and compared well to complimentary GC-MS data. Exchanging D2 O for CD3 OD as the solvent utilised for analysis resulted in a significantly lower amount of 4-PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.

中文翻译：

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SABER 超极化哌嗪类药物的台式 NMR 分析

哌嗪类药物，如 N-苄基哌嗪 (BZP)，由于具有类似于苯丙胺的作用，在 2000 年代变得有吸引力。在此，BZP 除了其吡啶基类似物外，还对 2-、3- 和 4-吡啶甲基哌啶（分别为 2-PMP、3-PMP 和 4-PMP）进行了超极化技术 SABRE（可逆交换信号放大）证明使用该技术检测这些基于哌嗪的药物。尽管 BZP 没有通过 SABRE 超极化，但 2-PMP、3-PMP 和 4-PMP 是，其中 4-PMP 的邻和间吡啶质子分别显示出 1.4 倍和 313 倍和 267 倍的最大增强T 检测场，跟随地球磁场的极化转移。除了游离碱之外，SABRE 还评估了 4-PMP.3HCl 并发现它不会极化，但是，添加增加当量的三乙胺 (TEA) 产生游离碱，在添加三当量 TEA 时观察到最大增强。进一步添加 TEA 导致观察到的增强减少。还使用 SABRE 极化模拟片剂中的 4-PMP.3HCl（约 20% w/w），以证明该技术的法医应用（邻吡啶质子增强 138 倍）。模拟片剂中存在的 4-PMP.3HCl 的量通过 NMR 进行定量，使用 D2O 作为溶剂，并与补充的 GC-MS 数据进行比较。将 D2 O 交换为 CD3 OD 作为用于分析的溶剂导致测定的 4-PMP.3HCl 的量显着降低，