Determination of zuclopenthixol and its main N-dealkylated metabolite in biological fluids using high-performance liquid chromatography with post-column photochemical derivatization and fluorescence detection.
A highly sensitive high-performance liquid chromatographic (HPLC) method for the assay of cis-(Z)-clopenthixol (zuclopenthixol) in urine and plasma has been developed. Following solid-phase extraction, the samples are chromatographed using reversed-phase ion-pairing HPLC. After separation, the solutes, having a thioxanthene structure, are transformed on-line into thioxanthones in a photochemical reactor. The thioxanthones are highly fluorescent compounds, and therefore, low detection limits are obtained when using fluorescence detection. Detection limits for zuclopenthixol and its N-dealkylated metabolite, in plasma as well as in urine, using fluorescence detection with excitation at 260 nm and emission at 435 nm, were found to be 0.05 ng/ml and 0.2 ng/ml, respectively. The chromatographic system separates the cis-(Z)- and trans-(E)-isomers of clopenthixol from its main dealkylated metabolite. Furthermore, the chromatographic system is very suitable for study of the photochemical reaction, since the chloro-thioxanthone and thioxanthone are well separated from the isomers of clopenthixol.
Hansen
B B
BB
Department of Analytical and Pharmaceutical Chemistry, Royal Danish School of Pharmacy, Copenhagen.
Hansen
S H
SH
D002851:Chromatography, High Pressure Liquid; D003006:Clopenthixol / Q000032:analysis* / Q000097:blood / Q000652:urine; D003640:Dealkylation; D006801:Humans; D010777:Photochemistry; D013050:Spectrometry, Fluorescence
D003006:Clopenthixol