Tianeptine: enantiomeric separations, structural assignment, and biological interactions.

Tianeptine is an atypical tricyclic antidepressant that has gained attention due to its unique mechanism of action, distinguishing it from other such medications. The drug has proliferated in recreational markets as "gas station heroin" since it produces opioid-like effects and euphoric highs as a result of binding to mu opioid receptors. The unrestricted availability of tianeptine has resulted in many irreversible adverse effects and fatal overdoses. Tianeptine is a chiral molecule and has not yet been widely investigated for the therapeutic/toxic effects of its single enantiomers. Such studies require reliable and fast chiral separation methods for separation and quantitation. In this study, the enantioselective HPLC methods in normal phase and polar ionic mode were developed for analytical and preparative separation and purification of tianeptine. Two chiral stationary phases were employed: one based on 1-(3,5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene and another based on a modified macrocyclic glycopeptide, both utilizing 2.7 μm core-shell bonded silica particles. These column chemistries are available under the commercial names of WhelkoShell and NicoShell, respectively. Both columns offer the same elution order, as confirmed by an optical circular dichroism detector. The absolute configurations of the purified single enantiomers were determined using vibrational circular dichroism spectroscopy with a 99 % confidence level. The total tianeptine and its enantiomeric ratio in recreational products were analyzed by HPLC-UV after developing a robust extraction procedure with ethanol for liquid and solid products. The assessment of the enantioselective binding of tianeptine to many essential proteins revealed higher affinity of human serum albumin for the S-tianeptine.