Development and validation of automated SPE‐HPLC‐MS/MS methods for the quantification of asenapine, a new antipsychotic agent, and its two major metabolites in human urine

Abstract

To support the evaluation of the pharmacokinetic parameters of asenapine (ASE) in urine, we developed and validated online solid-phase extraction high-performance liquid chromatography methods with tandem mass spectrometry detection (SPE-LC-MS/MS) for the quantification of ASE and two of its major metabolites, N-desmethylasenapine (DMA) and asenapine-N⁺-glucuronide (ASG). The linearity in human urine was found acceptable for quantification in a concentration range of 0.500-100 ng/mL for ASE and DMA and 10.0-3000 ng/mL for ASG, respectively.

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

“…To the best of our knowledge, just one paper has been published on SNP chiral separation, but using CE with unmodified β‐cyclodextrin and without biological application . On the other hand, some analytical methods have been published for the non‐enantioselective determination of SNP in biological matrices among which those designed for patient monitoring are very few and only one dealing with micromatrices . None of them was applied to real samples from psychiatric patients, nor have they compared different and novel dried microsampling approaches.…”

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

“…Plasma ASE and ASE‐G were determined in the concentration ranges of 0.025–20.0 and 0.25–50.0 ng/mL, respectively, using separate chromatographic methods (de Boer et al, ). The same approach was applied to estimate ASE and ASE‐G from human urine with a linear working range of 0.500–100 and 10.0–3000 ng/mL, respectively (de Boer et al, ). Methods to analyze PRO and PRO‐G are largely intended to study their disposition in rat plasma (Beaudry et al, ), horse plasma (Aramaki et al, ), human plasma (Luan et al, ) and various organs of mice such as brain, lung, kidney and liver (Salomonsson et al, ), with little information on quantitative analysis.…”

“…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, ).…”

Fast simultaneous LC/MS/MS determination of 10 active compounds in human serum for therapeutic drug monitoring in psychiatric medication

“…Antidepressants and antipsychotics have been analyzed by gas chromatography (Papoutsis et al ., ), but mainly by HPLC, for example, with UV (Zhang et al ., , b) or fluorescence detection (Suckow et al ., ), which are cheaper but require a large volume of blood sample (0.5 mL; Aravagiri et al ., ). Today, detection is performed preferably by mass spectrometry, rendering effective confirmation of analytes and sufficient LOQs, both important in bioanalysis (Patil et al ., ; de Boer et al ., ; Ansermot et al ., ; Vecchione et al ., ; Sampedro et al ., ). Ionization is usually carried out in positive mode using electrospray ionization (ESI+) (Zhang et al ., ; Hasselstrom, ; Vecchione et al ., ; Liang and Bartlett, ; Ambavaram et al ., ) more often than atmospheric pressure chemical ionization (APCI+) (Aravagiri et al ., ).…”