Metabolism studies of the antischistosomal drug praziquantel using tandem mass spectrometry: qualitative identification of 17 hydroxylated metabolites from mouse urine.
Schistosomiasis is a parasitic liver infection which is known to affect many aspects of drug metabolism. Praziquantel (PZQ) is the drug of choice for treating this disease. PZQ is known to be highly metabolized, but the effect of the disease on its metabolism has not been investigated. Control mice and mice infected with Schistosoma mansoni were dosed with PZQ and their urines were examined for the presence of metabolites using a triple-quadrupole mass spectrometer (tandem mass spectrometer). The collisionally induced dissociation of PZQ was remarkable in its structurally significant fragments. From this we were able to identify 17 hydroxylated metabolites of PZQ from purified urine samples without further chemical separation, including three monohydroxylated, six dihydroxylated, and eight trihydroxylated metabolites. There were no qualitative differences in metabolite production between control and infected animals.
Ali
M H
MH
Department of Pharmacology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037.
Fetterolf
D D
DD
Abramson
F P
FP
Cohn
V H
VH
D000818:Animals; D001711:Biotransformation; D004967:Estrogens / Q000032:analysis; D005260:Female; D006900:Hydroxylation; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D011223:Praziquantel / Q000378:metabolism* / Q000652:urine; D012555:Schistosomiasis mansoni / Q000378:metabolism; D012556:Schistosomicides / Q000378:metabolism*
D004967:Estrogens; D012556:Schistosomicides; D011223:Praziquantel