NMS Labs, 3701 Welsh Road, Willow Grove, PA 19090, USA.
Prescription Drug Research Center, LLC, 12728 Penguin Drive, Bradenton, FL 34212, USA.
J Pharm Biomed Anal. 2018 Jul 15;156:16-22. doi: 10.1016/j.jpba.2018.04.016. Epub 2018 Apr 16.
Clandestine chemists have demonstrated an ability to convert commercially available pseudoephedrine formulations to methamphetamine. Some of these formulations have properties that manufacturers claim limit or block the extraction of pseudoephedrine and its direct conversion to methamphetamine. In this study, 3 commercially available pseudoephedrine formulations were evaluated for ease of extraction and conversion to methamphetamine using a common chemistry technique called the one-pot method that is frequently employed by clandestine chemists. Two marketed pseudoephedrine formulations with claimed tamper-resistant properties - Zephrex-D and Nexafed - were compared to Sunmark, a comparator formulation of pseudoephedrine without tamper-resistant properties. Particle size reduction was conducted using 8 readily available tools; solubility was assessed using 2 common aqueous solutions and various reaction conditions (e.g., temperature, stirring); extractability was evaluated using 8 common organic solvents. The one-pot (single vessel) method commonly used in clandestine processes was employed; chemicals and equipment were purchased locally on the open market. Quantities and addition times of the chemicals used to carry out the procedure and the duration of the reaction were varied to determine the effect on methamphetamine yield. The procedure was appropriately scaled and conducted in a controlled environment to reduce risk and maximize yields. Pseudoephedrine and methamphetamine were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Standard quantitative procedures were used to determine the quantities of pseudoephedrine and methamphetamine recovered and produced, respectively. Particle size reduction resulted in some loss of material of each pseudoephedrine formulation; Zephrex-D tablets were broken down to a coarse material; Nexafed and Sunmark tablets were reduced to a fine powder. The solubility rates of intact and ground tablets varied by product; Zephrex-D was most resistant to solubilizing while Nexafed and Sunmark were comparable and dissolved completely, demonstrating no solubility-resistant properties. Conditions of the one-pot method were modified throughout the studies to increase methamphetamine yield. Using optimal parameters identified in these studies and allowing the reaction to proceed for 90 min, average percent conversions were similar for the 3 formulations: 43.3% for Zephrex-D, 46.4% for Nexafed, and 48.6% for Sunmark. The greatest conversion occurred with a 150 min reaction time and resulted in 44.8%-48.4% conversion of Zephrex-D, 54.1%-66.4% conversion of Nexafed, and 58.6%-71.8% conversion of Sunmark. This series of methodological evaluations demonstrated that clandestine chemists can readily produce similar yields of methamphetamine using pseudoephedrine products with and without claimed tamper-resistant technology.
秘密化学家已经证明能够将市售的伪麻黄碱制剂转化为甲基苯丙胺。其中一些制剂具有制造商声称的限制或阻止伪麻黄碱提取及其直接转化为甲基苯丙胺的特性。在这项研究中，使用一种称为一锅法的常用化学技术评估了 3 种市售的伪麻黄碱制剂，该技术经常被秘密化学家使用。两种具有抗篡改特性的市售伪麻黄碱制剂（Zephrex-D 和 Nexafed）与 Sunmark 进行了比较，Sunmark 是一种没有抗篡改特性的伪麻黄碱对照制剂。使用 8 种现成的工具进行粒径减小；使用 2 种常见的水溶液和各种反应条件（例如温度、搅拌）评估溶解度；使用 8 种常见的有机溶剂评估可提取性。在秘密过程中常用的一锅法（单个容器）进行；在公开市场上就地购买化学品和设备。改变进行该程序的化学品的用量和添加时间以及反应时间的长短，以确定对甲基苯丙胺产率的影响。适当放大该程序并在受控环境中进行，以降低风险并最大限度地提高产量。使用液相色谱-串联质谱法（LC-MS/MS）定量测定伪麻黄碱和甲基苯丙胺。使用标准定量程序分别确定回收和产生的伪麻黄碱和甲基苯丙胺的量。粒径减小导致每种伪麻黄碱制剂的部分材料损失；Zephrex-D 片剂分解为粗物质；Nexafed 和 Sunmark 片剂则被粉碎成细粉。完整和粉碎片剂的溶解速率因产品而异；Zephrex-D 最难溶解，而 Nexafed 和 Sunmark 则相似且完全溶解，没有显示出抗溶解特性。整个研究过程中都修改了一锅法的条件以提高甲基苯丙胺的产率。使用这些研究中确定的最佳参数，并允许反应进行 90 分钟，3 种制剂的平均转化率相似：Zephrex-D 为 43.3%，Nexafed 为 46.4%，Sunmark 为 48.6%。反应时间最长为 150 分钟，转化率最高，Zephrex-D 的转化率为 44.8%-48.4%，Nexafed 的转化率为 54.1%-66.4%，Sunmark 的转化率为 58.6%-71.8%。这一系列方法评估表明，秘密化学家可以使用具有和不具有声称的抗篡改技术的伪麻黄碱产品轻松地生产出相似产率的甲基苯丙胺。
