Loxapine (LOX) is a dibenzoxazepine neuroleptic drug used mainly for the treatment of schizophrenia. Loxapine is metabolized to amoxapine (AMX), 7-OH-Loxapine (7-OH-LOX) and 8-OH-Loxapine (8-OH-LOX).

As new therapeutic areas and routes of administration are explored for LOX, therapeutic concentrations could be achieved with a <1 mg dose of LOX. At these dose levels, LOX and metabolites could be near 0.05 ng/mL in human plasma 24 hours post dose.

Previous HPLC assays quantified LOX and metabolites but limits of quantitation >3 ng/mL were achieved. These assays also suffered from poor precision (>20% RSD) and long run times (>10 minutes/sample). Here we report on an accurate and precise LC/MS/MS assay for the determination of LOX, AMX, 7-OH-LOX and 8-OH-LOX from human plasma.