Study of Separation and Extraction Conditions for Five Neuroleptic Drugs by an LLE-HPLC-DAD Method in Human Plasma

Abstract

Separation and extraction conditions for four atypical neuroleptics (clozapine, N-desmethylclozapine (active metabolite of clozapine), olanzapine, and quetiapine) and one classical neuroleptic (perazine) in human plasma have been studied. Reverse phase chromatography (RP-18) with the mobile phase consisted of: A. aq. orthophosphoric acid with addition of N,N,N′,N′-tetramethylethylendiamine (TEMED), pH = 5.0, and B. acetonitrile, in gradient flow, was selected. As the optimal liquid-liquid extraction conditions, sample pH = 11.6, extraction system, ethyl acetate/n-hexane/isopropanol (16:3:1, v/v/v), and back extraction into 0.01% orthophosphoric acid were chosen.

Keywords:

• Antipsychotic drugs
• Atypical neuroleptics
• High performance liquid chromatography
• Human plasma
• Liquid–liquid extraction
• Phenothiazine neuroleptics

Notes

^a contaminations extracted from isoamyl alcohol did not enable to read olanzapine data (first peak on the chromatogram, Fig. 5).

^b LLE process was assisted by ultrasonic energy. The abbreviations of the drugs studied are the same as in Table 2.