Determination of haloperidol and its reduced metabolite in human plasma by liquid chromatography-mass spectrometry with electrospray ionization.
A sensitive and accurate liquid chromatographic-electrospray mass spectrometric (LC-ES-MS) method for the determination of haloperidol (H) and reduced haloperidol (RH) in human plasma is presented, using chlorohaloperidol as the internal standard. A 2-ml volume of plasma was subjected to basic (NaOH) extraction, acid (HCl) back-extraction, acid wash and basic (NaOH) re-extraction. The extraction solvent was hexane-isoamyl alcohol (99:1, v/v) for the whole procedure. A Nucleosil C18 column (150 x 1 mm) was used for high-performance liquid chromatography, together with 2 mM HCOONH4-acetonitrile (55:45, v/v; pH 3.0) as the mobile phase. For each drug, four characteristic ions were monitored. Linearity was assessed in the ranges 0.1-50 and 0.25-50 ng/ml for H and RH, respectively. Recoveries were 58 and 70% and detection limits were 0.075 and 0.100 ng/ml for H and RH, respectively. Correlation coefficients were better than 0.999 for both compounds. R.S.D.s for repeatability and reproducibility at 0.25 ng/ml were 11.1 and 8.5% for H and 9.4 and 11.2% for RH, respectively. One of the main advantages of (LC-ES-MS) over other detection systems is the increase in selectivity obtained by monitoring three ions of confirmation for each of the drugs.
Hoja
H
H
Service de Pharmacologie et Toxicologie, Chru Dupuytren, Limoges, France.
Marquet
P
P
Verneuil
B
B
Lotfi
H
H
Dupuy
J L
JL
Pénicaut
B
B
Lachâtre
G
G
D014150:Antipsychotic Agents / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D015203:Reproducibility of Results
D014150:Antipsychotic Agents; C040692:4-(4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl)-1-(4-fluorophenyl)-1-butanol; D006220:Haloperidol