Medicines and health products, Scientific Direction of Chemical and Physical Health Risks, Sciensano, Rue Juliette Wytsmanstraat 14, 1050 Brussels, Belgium; Department of In Vitro Toxicology and Dermato-Cosmetology (IVTD), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium.
Medicines and health products, Scientific Direction of Chemical and Physical Health Risks, Sciensano, Rue Juliette Wytsmanstraat 14, 1050 Brussels, Belgium.
J Pharm Biomed Anal. 2019 May 30;169:225-234. doi: 10.1016/j.jpba.2019.03.002. Epub 2019 Mar 2.
The electronic cigarette (e-cigarette) has emerged as a popular alternative to the traditional hazardous tobacco cigarette. The substantial increase in e-cigarette use also urgently calls for controlling the quality of e-cigarette refill liquid products (e-liquids). Currently, the most important quality indicator of e-liquid products is the quantification of nicotine and its related impurities. Although different methods have been published to measure nicotine and impurity levels, the majority of them use a targeted LC-MS/MS approach. There is, however, a need for more robust quantification methods that are easy to implement in most control (industrial and governmental) laboratories. Therefore, in this study, a simple dilute-and-shoot UHPLC-DAD method has been developed and validated for the simultaneous quantification of nicotine and its alkaloid impurities in electronic cigarette refills. An optimal separation of the alkaloids was achieved in a runtime of 11 min. The method was successfully validated using the "total error" approach in accordance with the validation requirements of ISO-17025. During this validation, interference between the target components and a number of popular flavouring compounds such as vanillin, maltol, ethylacetate, etc. could be excluded. In addition, small changes to the column temperature, pH and molar concentration of the mobile phase buffer were deliberately introduced in order to assess the robustness of the method. Only a slightly different outcome between the newly developed UV-detection method and the targeted MS approach was found, due to the sensitivity of the different detection techniques. However, in the context of quality control of nicotine related impurities, for which the European Pharmacopoeia limits are currently applied, the sensitivity of the UHPLC-DAD method was found to be within the acceptable range. Despite the somewhat lower selectivity of the newly developed UV-detection technique versus a targeted LC-MS/MS approach, it may be concluded that this method is a suitable alternative for quality control purposes.
电子烟作为传统危险烟草香烟的替代品已经变得非常流行。电子烟的使用量大幅增加，也迫切需要控制电子烟补充液产品（电子烟液）的质量。目前，电子烟液产品最重要的质量指标是尼古丁及其相关杂质的定量。虽然已经发表了不同的方法来测量尼古丁和杂质水平，但大多数方法都使用靶向 LC-MS/MS 方法。然而，需要更稳健的定量方法，这些方法易于在大多数控制（工业和政府）实验室中实施。因此，在这项研究中，开发并验证了一种简单的稀释-进样 UHPLC-DAD 方法，用于同时定量电子烟液中的尼古丁及其生物碱杂质。在 11 分钟的运行时间内，实现了生物碱的最佳分离。该方法通过按照 ISO-17025 的验证要求使用“总误差”方法成功地进行了验证。在验证过程中，可以排除目标成分与香草醛、麦芽醇、乙酸乙酯等许多流行调味化合物之间的干扰。此外，还故意改变柱温、pH 值和流动相缓冲液的摩尔浓度，以评估方法的稳健性。由于不同检测技术的灵敏度，新开发的 UV 检测方法与靶向 MS 方法之间的结果略有不同。然而，在与欧洲药典目前应用的尼古丁相关杂质质量控制相关的情况下，发现 UHPLC-DAD 方法的灵敏度在可接受范围内。尽管与靶向 LC-MS/MS 方法相比，新开发的 UV 检测技术的选择性略低，但可以得出结论，该方法是质量控制目的的合适替代方法。
