High throughput identification and quantification of 16 antipsychotics and 8 major metabolites in serum using ultra-high performance liquid chromatography-tandem mass spectrometry

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• 作者：Lisbeth Patteet ; Kristof E. Maudens ; Bernard Sabbe ; Manuel Morrens ; Mireille De Doncker ; Hugo Neels
• 关键词：7OH-NDA-QUE ; 7-hydroxy-N-desalkyl-quetiapine ; 7OH-QUE ; 7-hydroxy-quetiapine ; AMI ; amisulpride ; AP ; antipsychotics ; AGNP ; Arbeidsgemeinschaft fü ; r Neuropsychopharmakologie und Pharmakopsychiatrie ; ARI ; aripiprazole ; ASE ; asenapine ; BRO ; bromperidol ; CLO ; clozapine ; CI ; confidence interval ; DARI ; dehydro-aripiprazole ; ESI ; electrospray ionization ; EMA ; European Medicines Agency ; ER ; extraction recovery ; FDA ; Food and Drug Administration ; HAL ; haloperidol ; HILO ; hydroxy-iloperidone ; ILO ; iloper
• 刊名：Clinica Chimica Acta
• 出版年：15 February, 2014
• 年：2014
• 卷：429
• 期：Complete
• 页码：51-58
• 全文大小：481 K

文摘

Background

Therapeutic drug monitoring of antipsychotics is important for optimizing therapy, explaining adverse effects, non-response or poor compliance. We developed a UHPLC-MS/MS method for quantification of 16 commonly used and recently marketed antipsychotics and 8 metabolites in serum.

Methods

After liquid-liquid extraction using methyl tert-butyl ether, analysis was performed on an Agilent Technologies 1290 Infinity LC system coupled with an Agilent Technologies 6460 Triple Quadrupole MS. Separation with a C18 column and gradient elution at 0.5 mL/min resulted in a 6-min run-time. Detection was performed in dynamic MRM, monitoring 3 ion transitions per compound. Isotope labeled internal standards were used for every compound, except for bromperidol and levosulpiride.

Results

Mean recovery was 86.8%. Matrix effects were 鈭?#xA0;18.4 to + 9.1%. Accuracy ranged between 91.3 and 107.0% at low, medium and high concentrations and between 76.2 and 113.9% at LLOQ. Within-run precision was < 15% (CV), except for asenapine and hydroxy-iloperidone. Between-run precision was aberrant only for 7-hydroxy-N-desalkylquetiapine, asenapine and reduced haloperidol. No interferences were found. No problems of instability were observed, even for olanzapine. The method was successfully applied on patient samples.

Conclusions

The liquid-liquid extraction and UHPLC-MS/MS technique allows robust target screening and quantification of 23 antipsychotics and metabolites.