Ionic Liquids as Separation Enhancers of Haloperidol and Its Two Metabolites in High-Performance Thin-Layer Chromatography Supported with Mass Spectrometry

Summary

High-performance thin-layer chromatography (HPTLC)–densitometric method of haloperidol (HP) and its two metabolites (reduced haloperidol [RHP], 4-(4-chlorophenyl)-4-hydroxypiperidine [CPHP]) from human plasma has been developed by use of mobile-phase additives. The influence of the type of inorganic/ organic additive on the retention of the studied compounds was evaluated. The chromatographic process was carried out with traditional mobile phase modifiers and 1-alkyl-imidazolium ionic liquid as separation enhancers, in the presence of chlorpromazine as internal standard. 1-Ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF₄]) ionic liquid offered good selectivity in comparison with traditional mobile phase additives. The studied drugs were well distributed as the R_F values were 0.31 for chlorpromazine hydrochloride (CPZ), 0.38 for HP, 0.44 for CPHP, and 0.58 for RHP, respectively, with no apparent broadening and overlapping of spots. The test compounds were extracted using acetonitrile as precipitation agent. The identity of the bands from human plasma was additionally confirmed by rapid and contamination-free CAMAG thin-layer chromatography–mass spectrometry (TLC–MS) interface. The limit of detection (LOD) values obtained by densitometry scanning were 0.1807, 0.3158, and 0.3924 μg spot⁻¹ (for HP, RHP, and CPHP), whereas the limit of quantification (LOQ) values for the presented method were 0.5476, 0.9570, and 1.1892 μg spot⁻¹ (for HP, RHP, and CPHP). Recovery values of all tested compounds were in the range from 95.43% to 99.60% (intra-day) and 96.13% to 103.18% (inter-day); %RSD did not exceed the value of 5%. The results confirm the positive effect of ionic liquids in the separation process related to their silanol blocking properties and their suitability for use in thin-layer chromatography/mass spectrometry method.