Synthetic cathinones, such as methylone and pentedrone, are psychoactive derivatives of cathinone, sold in the internet as “plant food” or “bath salts”.

However, the level at which these compounds and their enantiomers cross the intestinal barrier has not been yet determined. Thus, the present study aimed to analyze the enantioselectivity on the permeability of these drugs through the intestinal barrier by using the Caco-2 cell line, a widely used in vitro model for drug permeability studies. To achieve this goal, an UHPLC-UV method was developed and validated to quantify both synthetic cathinones.

The developed UHPLC-UV method revealed high selectivity and a linearity from 1 to 500 μM with correlation coefficients always higher than 0.999. The method has an accuracy that ranged between 89 and 107%, inter-day and intra-day precisions with coefficients of variation below 10%, limits of detection and quantification of 0.31 μM and 0.93 μM for methylone and 0.17 μM and 0.52 μM for pentedrone, respectively. In Caco-2 cells, a differentiated passage of the enantiomers across monolayer was observed for both cathinones. For pentedrone, the difference was observed after the first hour, being R-(−)-pentedrone the most permeable compound. Regarding methylone, the difference was noted after one hour and 30 min, with S-(−)-methylone being the most absorbed enantiomer.

In conclusion, a fully validated method was successfully applied for studying the permeability of methylone and pentedrone enantiomers in an in vitro model of human intestine, which allowed to discover, for the first time, the enantioselectivity in drug permeability of this class of drugs.

合成的卡西酮，如甲酮和戊二酮，是卡西酮的精神活性衍生物，在互联网上以“植物性食品”或“沐浴盐”出售。

然而，尚未确定这些化合物及其对映异构体穿过肠屏障的水平。因此，本研究旨在通过使用广泛用于药物渗透性研究的体外模型Caco-2细胞系来分析这些药物通过肠屏障的渗透性的对映选择性。为实现此目标，开发并验证了UHPLC-UV方法以定量两种合成的卡西酮。

所开发的UHPLC-UV方法显示出高选择性和1至500μM的线性，相关系数始终高于0.999。该方法的准确度在89％至107％之间，日间和日内精度，变异系数低于10％，甲酮的检出限和定量限为0.31μM和0.93μM，戊二酮的检出限为0.17μM和0.52μM ， 分别。在Caco-2细胞中，两种卡西酮均观察到对映异构体跨单层的分化传代。对于戊酮，在第一小时后观察到差异，R -（-）-戊酮是最易渗透的化合物。关于甲酮，在1小时30分钟后观察到差异，其中S -（-）-甲酮是吸收最强的对映异构体。

总而言之，一种经过充分验证的方法已成功地用于研究人肠体外模型中甲酮和戊二酮对映体的渗透性，这首次发现了此类药物在药物渗透性方面的对映选择性。