Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography.
Loxapine, its N-demethylated metabolite amoxapine, and their 7- and 8-hydroxy metabolites were determined simultaneously in plasma by a simple two-step extraction procedure followed by reversed-phase liquid chromatography. Baseline separation was achieved by a 5-microns Spherisorb C6 column. The mobile phase consisted of 5 mM phosphate buffer (with 14 mM orthophosphoric acid)-acetonitrile (with 105 microM nonylamine) (77:23, v/v). Assays of the steady-state plasma samples obtained from seventeen patients on loxapine showed substantial amounts of 8-hydroxy metabolites, lesser amounts of loxapine, amoxapine and 7-hydroxyloxapine and trace amounts of 7-hydroxyamoxapine. As 8-hydroxy metabolites possess only weak dopamine-D2 blocking activity, the final neuroleptic property of loxapine may be affected significantly by metabolic polymorphism.
Cheung
S W
SW
Psychopharmacology Unit, Clarke Institute of Psychiatry, Toronto, Canada.
Tang
S W
SW
Remington
G
G
D000657:Amoxapine / Q000097:blood*; D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D003342:Corpus Striatum / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008152:Loxapine / Q000031:analogs & derivatives / Q000097:blood*; D051381:Rats; D013134:Spiperone / Q000378:metabolism
D013134:Spiperone; C035233:8-hydroxyloxapine; D008152:Loxapine; D000657:Amoxapine