Picogram determination of iloperidone in human plasma by solid-phase extraction and by high-performance liquid chromatography-selected-ion monitoring electrospray mass spectrometry.
A very sensitive liquid chromatographic-mass spectrometric (LC-MS) method has been developed to quantitate iloperidone, 1, and its principal metabolite, 4-[3-[4-(6-fluoro-1,2- benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-alpha- methylbenzenemethanol, 2, in human plasma. Iloperidone is currently used in clinical trials for the treatment of psychoses. The analytes were extracted from human plasma using mixed-mode Bond-Elut Certify cartridges and quantitated using selected-ion monitoring electrospray ionization mass spectrometery (SIM-ES-MS). No interference was observed from endogenous compounds following the extraction of plasma samples from six different human subjects. The limit of quantitation for 1 and 2 was 250 pg/ml of plasma. The standard curves were linear over a working range of 250 pg to 20 ng/ml. Absolute recoveries from plasma ranged from 82 to 101% and 73 to 97% for 1 and 2, respectively. Overall intra-day precision ranged from 0 to 9% and 0.9 to 12.5% for 1 and 2, respectively. The method was found to be rugged and very reliable due to the high specificity of SIM-ES-MS. The results obtained from this study confirm the application of solid-phase extraction combined with SIM-ES-MS in quantitating basic drugs in small quantities in biological extracts.
Mutlib
A E
AE
Department of Chemical Research, Hoechst-Roussel Pharmaceuticals Inc., Somerville, NJ 08876, USA.
Strupczewski
J T
JT
D014150:Antipsychotic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007555:Isoxazoles / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods*; D010880:Piperidines / Q000097:blood*; D015203:Reproducibility of Results
D014150:Antipsychotic Agents; D007555:Isoxazoles; D010880:Piperidines; C081732:iloperidone