Selective Depletion of Chiral 4-Hydroxypraziquantel Metabolites in Three Types of Aquaculture Fish by LC-MS/MS

Abstract

The rise of aquaculture has necessitated the use of antibiotics and other agents in these densely populated and often closed environments. An enantioselective depletion study of four chiral 4-hydroxypraziquantel metabolites (4-OH-PZQ) in perch, tilapia, and ricefield-eel muscles was done using a simple, sensitive, and reliable liquid-chromatography−tandem-massspectrometry (LC-MS/MS) method. These metabolites result from the uptake of the drug praziquantel (PZQ), which is used in aquaculture. A novel strategy of using a C 18 short column in tandem with a chiral hydroxypropyl-β-cyclodextrin superficially porous particle (CDShell-RSP) column produced the optimal separation for both the enantiomers and diastereoisomers of 4-OH-PZQ. The method was linear over the concentration range of 1−250 μg L −1 (r 2 ≥ 0.99) for R-trans-4-OH-PZQ, S-trans-4-OH-PZQ, R-cis-4-OH-PZQ, and S-cis-4-OH-PZQ. The average recoveries of four analytes at three spiked levels of 1, 10, and 100 μg kg −1 ranged from 84.2 to 93.1%, and the intraday and interday relative standard deviations were less than 7.9%. The limits of quantification of the four 4-OH-PZQ metabolites in perch-, tilapia-, and ricefield-eel-muscle matrices were 1.0 μg kg −1 . The method was utilized to monitor the depletion of trans-and cis-4-OH-PZQ enantiomers in perch, tilapia, and ricefield-eel muscle following oral administration (medicine bath for ricefield eel). Species-specific differences in the PZQ metabolism of isomers were observed. In addition, new metabolites of PZQ were observed: 3-hydroxypraziquantel diastereomers.

Stereoselective Pharmacokinetics and Residue Depletion of Praziquantel and Its Metabolites, 4-Hydroxypraziquantel Enantiomers, in Swine

“…Our pretreatment methods followed previously published protocols ,, and are briefly described below.…”

“…Stereoselective Pharmacokinetics of PZQ and 4-OH-PZQ Enantiomers. It should be noted that, although the strategy of using a C 18 tandem HP-RSP chiral column could effectively separate achiral and chiral isomers of PZQ and 4-OH-PZQ, an unknown metabolite (3-OH-PZQ) 22 was observed between Strans-4-OH-PZQ and R-cis-4-OH-PZQ in real swine plasma and tissue samples. The actual metabolites of PZQ in vivo are complex.…”

“…Both studies revealed that residue elimination rates of R -PZQ and S -PZQ in perch muscle were the same; i.e., there was no difference in stereoselectivity. Additionally, Zhang et al revealed species-specific differences in isomer metabolism of trans -4-OH-PZQ and cis -4-OH-PZQ in the muscles of perch, tilapia, and ricefield eel.…”

“…However, S - trans -4-OH-PZQ and R - cis -4-OH-PZQ could not be separated, and the two enantiomers of cis -4-OH-PZQ did not reach a baseline separation. Zhang et al successfully established an LC-MS/MS approach to analyze the residues of PZQ, trans -4-OH-PZQ, cis -4-OH-PZQ, and their enantiomers in fish using a tandem strategy comprised of a C 18 column and a chiral column and achieved baseline separation of the four diastereomers and enantiomers of 4-OH-PZQ. Thus far, there have been no reports on the evaluation of PZQ and its primary metabolites’ enantiomers, namely trans -4-OH-PZQ and cis -4-OH-PZQ, in the plasma and edible tissues of swine.…”

“…Numerous reports have explored the pharmacokinetics and residue elimination of PZQ and its main metabolite enantiomers in vivo , primarily focusing on human and animal plasma ,, and aquatic animals. , However, there is a lack of research concerning the pharmacokinetics and residue depletion of PZQ, trans -4-OH-PZQ, cis -4-OH-PZQ, and their corresponding enantiomers in swine. Consequently, in the present study, we developed an LC-MS/MS method to separate and determine the enantiomers of PZQ and its main metabolites ( trans -4-OH-PZQ and cis -4-OH-PZQ) in swine plasma and 10 tissues (muscle, fat, liver, kidney, spleen, heart, lung, small intestine, large intestine, and stomach).…”