Validation of HPLC-MS/MS methods for analysis of loxapine, amoxapine, 7-OH-loxapine, 8-OH-loxapine and loxapine N-oxide in human plasma.
BACKGROUND
Two ESI-LC-MS/MS methods were validated for the quantitative analysis of loxapine, amoxapine, 7-OH-loxapine, 8-OH-loxapine and loxapine N-oxide in human K(2)EDTA plasma. Cation-exchange solid-phase extraction (SPE) was used to extract loxapine, amoxapine and the two hydroxylated metabolites, and organic precipitation was used to quantify loxapine N-oxide.


RESULTS
Both methods were shown to be accurate (±13%), intra-assay precision was less than 15%, and inter-assay precision was less than 10% in all instances across the entire dynamic range of the assays (0.0500-50.0 ng/ml for the SPE method and 0.100-25.0 ng/ml for the precipitation method).


CONCLUSIONS
The validated methods for loxapine, amoxapine, 7-OH-loxapine, 8-OH-loxapine and loxapine N-oxide have been used to successfully support clinical trials.
Alturas Analytics, Inc., 1324 Alturas Drive, Moscow, ID 83843, USA. jzimmer@alturasanalytics.com
Jennifer S D
JS
Zimmer
Shane R
SR
Needham
Chad D
CD
Christianson
Crystal M
CM
Piekarski
Chrystal N
CN
Sheaff
Keith
K
Huie
Andrea R
AR
Reed
Lori
L
Takahashi
D000657:Amoxapine / Q000097:blood / Q000378:metabolism; D014150:Antipsychotic Agents / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003497:Cyclic N-Oxides / Q000097:blood* / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008152:Loxapine / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods
D014150:Antipsychotic Agents; D003497:Cyclic N-Oxides; D008152:Loxapine; D000657:Amoxapine