Determination of asenapine in presence of its inactive metabolites in human plasma by LC-MS/MS

Abstract

A highly selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been described for the determination of asenapine (ASE) in presence of its inactive metabolites N-desmethyl asenapine (DMA) and asenapine-N-glucuronide (ASG). ASE, and ASE 13C-d3, used as internal standard (IS), were extracted from 300 µL human plasma by a simple and precise liquid-liquid extraction procedure using methyl tert-butyl ether. Baseline separation of ASE from its inactive metabolites was achieved on Chromolith Performance RP8e (100 mm × 4.6 mm) column using acetonitrile-5.0 mM ammonium acetate-10% formic acid (90:10:0.1, v/v/v) within 4.5 min. Quantitation of ASE was done on a triple quadrupole mass spectrometer equipped with electrospray ionization in the positive mode. The protonated precursor to product ion transitions monitored for ASE and ASE 13C-d3 were m/z 286.1 → 166.0 and m/z 290.0 → 166.1, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) of the method were 0.0025 ng/mL and 0.050 ng/mL respectively in a linear concentration range of 0.050–20.0 ng/mL for ASE. The intra-batch and inter-batch precision (% CV) and mean relative recovery across quality control levels were ≤ 5.8% and 87.3%, respectively. Matrix effect, evaluated as IS-normalized matrix factor, ranged from 1.03 to 1.05. The stability of ASE under different storage conditions was ascertained in presence of the metabolites. The developed method is much simpler, matrix free, rapid and economical compared to the existing methods. The method was successfully used for a bioequivalence study of asenapine in healthy Indian subjects for the first time.

Densitometry and indirect normal‐phase HPTLC–ESI–MS for separation and quantitation of drugs and their glucuronide metabolites from plasma

“…The proposed method was adequately sensitive to monitor the plasma concentration of these drugs up to 48 h. The maximum plasma concentration ( C max ) and time to reach maximum concentration ( T max ) for ASE, ASE‐G, PRO, PRO‐G, TEL and TEL‐G were 5.21 ng/mL and 0.62 h; 8.62 ng/mL and 2.42 h; 74.5 ng/mL and 1.92 h; 423.6 ng/mL and 2.11 h; 364.3 ng/mL and 0.95 h; and 44.6 ng/mL and 1.10 h, respectively. The results obtained for all the three drugs were in good agreement with reported studies in healthy subjects (de Boer et al, ; Midha et al, ; Patel et al, ; Stangier et al, ).…”

“…In the present work an attempt is made to separate and quantify three selected drugs, namely asenapine (ASE), propranolol (PRO) and telmisartan (TEL) and their phase II glucuronide metabolites (Figure ) using TLC–densitometry and indirect sampling HPTLC–MS. The literature presents few methods to study these drug–metabolite pairs using LC–MS/MS (Aramaki, Mori, Nakata, Shinohara, & Koizumi, ; Beaudry et al, ; de Boer et al, ; de Boer et al, ; Kertesz & Van Berkel, ; Li et al, ; Luan, Shao, Ma, & Zeng, ; Patel et al, ; Salomonsson, Bondesson, & Hedeland, ). ASE and asenapine‐ β ‐ d ‐glucuronide (ASE‐G) along with other metabolites have been determined in human plasma (de Boer et al, ) and urine (de Boer et al, ).…”

“…ASE and asenapine‐ β ‐ d ‐glucuronide (ASE‐G) along with other metabolites have been determined in human plasma (de Boer et al, ) and urine (de Boer et al, ). Another study reports the determination of ASE in human plasma after chromatographic separation from its metabolites (Patel et al, ). Metabolite profiling of PRO metabolites has been reported from urine samples of adult male Sprague–Dawley rats (Beaudry et al, ).…”

PES, molecular structure, spectroscopic (FT-IR, FT-Raman), electronic (UV-Vis, HOMO-LUMO), quantum chemical and biological (docking) studies on a potent membrane permeable inhibitor: dibenzoxepine derivative

“…In addition, dibenzoxepines and pyrrole derivatives play an essential role in wide range of biological activities such as DNA binding, antimicrobial, antioxidant, enzyme/receptor interactions, antidepressant, bipolar disorder, plasma therapy etc. [ 1 , 2 , 3 , 4 , 5 ]. 5TDOP compound has heterocyclic intermediate substituent pyrrole which is widely used in pharmaceuticals [ 2 ], production of agrochemicals, synthesis of dyes, photographic chemicals etc.…”

Fabrication of Highly Sensitive Electrochemical Sensor Based on Chromium-Doped Ferrite Nanoparticles: Hybrid Graphene Nanosheets for the First Voltammetric Determination of Asenapine Maleate in Formulations and Human Plasma

“…Asenapine (ASE) is applied in the treatment of manic and schizophrenia. 1 ASE can also help in removal of the negative impact of symptoms as well as upgrade cognitive function for schizophrenia patient. 2 Asenapine has particular human receptor, with antagonistic properties than those of antipsychotic drugs.…”