Simultaneous determination of aripiprazole and its active metabolite, dehydroaripiprazole, in plasma by capillary electrophoresis combining on‐column field‐amplified sample injection and application in schizophrenia

Abstract

A sensitive high-performance CZE combining on-column field-amplified sample injection (FASI) has been developed for simultaneous determination of aripiprazole and its active metabolite, dehydroaripiprazole, in human plasma. A sample pretreatment by means of liquid-liquid extraction (LLE) (diethyl ether) with subsequent quantitation by FASI-CZE was used. The separation of aripiprazole and dehydroaripiprazole was performed using a BGE containing 150 mM phosphate buffer (pH 3.5) with 40% methanol and 0.02% PVA as a dynamic coating to reduce interaction of analytes with the capillary wall. Before sample loading, a methanol plug (0.3 psi, 6 s) was injected to permit FASI for stacking. The samples were injected electrokinetically (10 kV, 30 s) to introduce sample cations and the applied voltage was 20 kV with on-column detection at 214 nm. Several parameters affecting the separation and sensitivity of the drug and its active metabolite were studied, including reconstitution solvent, organic modifier, pH and concentration of phosphate buffer. The linear ranges of the method for test drug and its active metabolite, in plasma using amlodipine as an internal standard, were over the range 5.0-100.0 ng/mL. One female volunteer (25 years old) was orally administered a single dose of 10 mg aripiprazole (Abilify, Otsuka) and blood samples were drawn over a 60 h period for pharmacokinetic study. The method was also applied to monitor the concentration of aripiprazole and dehydroaripiprazole in plasma collected after oral administration of 20 or 30 mg aripiprazole (Abilify, Otsuka) daily at steady state in one schizophrenic patient.

Sensitive determination of aripiprazole using chemiluminescence reaction of tris(1,10-phenanthroline)ruthenium(ii) with acidic Ce(iv)

“…All other methods have a narrower linear dynamic range, lower throughput and are less sensitive than the proposed method. Analytical techniques coupled with a separation method, [7][8][9]13,15,[19][20][21]28,29 besides chemical information for ARP, provide multi-analyte information about related species, compounds and metabolites present in the sample. However, each of these methods oen offers its own set of advantages and disadvantages.…”

On‐line sample concentration via micelle to solvent stacking of cations prepared with aqueous organic solvents in capillary electrophoresis

“…The SEFs calculated using the LOD were from 41 to 68 (see Table ). The LODs for similar antipsychotic drugs by CE with stacking found in literature were better however, the reported methods required off‐line sample concentration .…”

Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2010–2012)

“…Because of their simplicity and ease of use, FASS can be combined with off‐line pre‐concentration techniques such as liquid–liquid extraction (LLE) , SPE , solvent–bar microextraction and dispersive liquid–liquid microextraction . Further, FASI can be used in combination with many different types of detection methods, and over the last two years have been used with fast‐scan cyclic voltammetry detection , capacitively coupled contactless conductivity detection (C 4 D) and electrochemiluminescence detection .…”