Enantioseparation and determination of asenapine in biological fluid micromatrices by HPLC with diode array detection

Abstract

Asenapine is a recent drug approved in the European Union for the treatment of bipolar disorder. An original approach has been developed for asenapine analysis in patients treated with the drug, including miniaturized microsampling procedures, separation and quantitation of drug enantiomers. An original enantioselective method based on high-performance liquid chromatography with diode array detection was developed and applied to the determination of asenapine enantiomer levels in innovative haematic samples: four micromatrices have been tested, two based on dried matrix spots (dried blood spots and dried plasma spots) and two based on volumetric absorptive microsampling (from blood and plasma). Chiral separation was achieved on a cellulose-tris(3,5 dimethylphenylcarbamate) column, with a mobile phase containing bicarbonate buffer and acetonitrile. The method was validated with satisfactory results of linearity and precision on all matrices that showed also a significant performance in terms of stability, feasibility and reliability, when compared to fluid plasma sampling, handling and processing. Among micromatrices, both volumetric absorptive microsampling types were superior to dried matrix spots in terms of data reproducibility and correspondence with plasma levels. The bioanalytical approach proposed herein provides for the first time a chiral high-performance liquid chromatographic method for the determination of asenapine enantiomers, coupled to a very effective microsampling strategy.

Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption

“…Usually, raw analytical data from plasma-based matrices can be used as such for quantitation and chemical-clinical correlations [41][42][43][44], while those obtained from blood-based matrices have to be elaborated to account for analyte dilution (correlated to hematocrit), and for red blood cell/plasma partitioning [45][46][47][48][49]. For the samples presented here, no direct hematocrit measurement was carried out: fixed hematocrit values were used, equal to 38% for females and 48% for males.…”

Preparation and evaluation of a deoxycholic‐calix[4]arene hybrid‐type receptor as a chiral stationary phase for HPLC

“…in dry CH 2 Cl 2 at 0 • C and the reaction was allowed to proceed for 12 h at room F I G U R E 5 Comparison of the differential free energies of enantioselective binding (ΔΔG) for the racemates, observed on CSP1 and CSP2 temperature. 1…”

“…The detection and separation of enantiomers in racemic mixtures is of great importance for scientists, as each enantiomer in a racemic mixture may show different toxicity, as well as different behavior in biological systems. Among various available analytical techniques for this purpose, HPLC seems to be the most popular and the most efficient technique to analyze racemic mixtures and to obtain enantiopure compounds . New HPLC chiral stationary phases (CSPs) with high chiral recognition for the separation of chiral molecules with varying structural properties are being introduced every day .…”

“…The detection and separation of enantiomers in racemic mixtures is of great importance for scientists, as each enantiomer in a racemic mixture may show different toxicity, as well as different behavior in biological systems. Among various available analytical techniques for this purpose, HPLC seems to be the most popular and the most efficient technique to analyze racemic mixtures and to obtain enantiopure compounds [1][2][3][4][5]. New HPLC chiral stationary phases (CSPs) with high chiral recognition for the separation of chiral molecules with varying structural properties are being introduced every Abbreviations: AIBN, Azobisisobutyronitrile; CSP, chiral stationary phase; DCM, dichloromethane; DEA, diethylamine; DNB-DL-leucine, N-(3,5-dinitrobenzoyl)-DL-leucine; DNB-DL-valine, N-(3,5-dinitrobenzoyl)-DL-valine; DNB, N- (3,5-dinitrobenzoyl); EtOH, ethanol; HOAc, acetic acid; IPA, 2-propanol; MeOH, methanol; TFA, trifluoroacetic acid; THF, tetrahydrofuran Conflict of interest: The authors have declared no conflict of interest.…”

Multiplexed therapeutic drug monitoring of antipsychotics in dried plasma spots by LC‐MS/MS

“…Classically, liquid whole blood, serum or plasma samples (LPs) (obtained from brachial venipuncture) are employed in the TDM of antipsychotics and concentration reference ranges are available for the interpretation of TDM results [2]. Recently, dried blood (DB), serum, or dried plasma (DP) spot samples have been shown as convenient alternatives to conventional liquid samples for drug measurement [15‐31]. They are easier to collect (even by a self‐directed simple finger pricking), easier to conserve, and to ship abroad because they do not require refrigeration, since analyte degradation is minimized in the absence of water [16].…”