Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Simultaneous Determination of Antipsychotic Drugs in Human Plasma and Its Application in Therapeutic Drug Monitoring.

We developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous therapeutic drug monitoring (TDM) and clinical pharmacokinetic antipsychotic drugs: clozapine (CLP), chlorpromazine (CPZ), risperidone (RPD), paliperidone (PLD), quetiapine (QTP;), aripiprazole (APZ), dehydroaripiprazole (DAP), olanzapine (OZP), ziprasidone (ZRD), and amisulpride (ASP). Analytes and internal standards (ISs) were separated using a Phenomenex phenyl-hexyl column (50.0 × 2.1 mm, 1.7 μm) with water containing 0.1% formic acid and 2 mM ammonium acetate, and methanol containing 0.1% formic acid and 2 mM ammonium acetate as the mobile phase. The antipsychotic drugs and ISs were extracted from 50 μL of plasma using acetonitrile. The calibration ranges were 25.0-1500.0 ng/mL for CLP, CPZ, DAP, and QTP, 10.0-600.0 ng/mL for CPZ and ZRD, 2.5-150.0 ng/mL for RPD, 5.0-300.0 ng/mL for PLD and OZP, and 20.0-1200.0 ng/mL for ASP. Validation was carried out according to the guidelines for bioanalytical validation, including assessment of calibration curves, specificity, accuracy, precision, recovery, stability, dilution integrity, and matrix effect. All the results satisfied the requirements. The results provided significant information to support future clinical TDM and rational drug use research. The proposed method also provided a simple, reliable, specific, and suitable technique for TDM and pharmacokinetic studies.

Qi Y ，Liu G 《Drug Design Development and Therapy》

Simple and Accurate Quantitative Analysis of 16 Antipsychotics and Antidepressants in Human Plasma by Ultrafast High-Performance Liquid Chromatography/Tandem Mass Spectrometry.

Wang J ，Huang H ，Yao Q ，Lu Y ，Zheng Q ，Cheng Y ，Xu X ，Zhou Q ，Wu D ，Zhang M ，Li X ，Zhang J ... -  《-》

Ultra-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 12 anti-tumor drugs in human plasma and its application in therapeutic drug monitoring.

The effectiveness and safety of anti-tumor drugs are clinically important issues, and their therapeutic drug monitoring (TDM) is recommended. This study aimed to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous TDM and exploration of clinical pharmacokinetics of anti-tumor drugs, including cyclophosphamide, ifosfamide, cisplatin, methotrexate, pemetrexed disodium, capecitabine, 5-fluorouracil, gemcitabine, doxorubicin, fulvestrant, tamoxifen, and irinotecan. After magnetic solid-phase extraction of plasma samples, the isotope internal standards and 12 anti-tumor drugs were separated using a ZORBAX Eclipse Plus C18 column (50.0 × 2.1 mm, 1.7 µm) with water containing 0.1% formic acid and acetonitrile as the mobile phase in a total run time of 5.0 min. The developed UPLC-MS/MS method was validated based on the Chinese Pharmacopoeia and the US Food and Drug Administration guidelines for bioanalytical method validation, including assessment of specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity, incurred sample reanalysis, and matrix effect. The results showed that a simple, fast, reliable, and specific UPLC-MS/MS method was developed and validated, and all the performance characteristics of the method met the requirements. The response function was established for concentration range of 0.10-25.00 μg/mL for gemcitabine, cyclophosphamide, ifosfamide, methotrexate, pemetrexed disodium, capecitabine, 5-fluorouracil, and cisplatin, and 0.05-12.50 μg/mL for doxorubicin, fulvestrant, tamoxifen, and irinotecan, with a coefficient of correlation of>0.9984 for all the compounds. The precision and accuracy of all the analytes were<6.5% and 5.9%, respectively. Hence, it could be used for TDM and exploration of pharmacokinetics of the aforementioned 12 anti-tumor drugs.

Li G ，Zhao M ，Zhao L 《-》

Simultaneous determination of clozapine, olanzapine, risperidone and quetiapine in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry.

Zhou Z ，Li X ，Li K ，Xie Z ，Cheng Z ，Peng W ，Wang F ，Zhu R ，Li H ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》

Development of a UPLC-MS/MS method for routine therapeutic drug monitoring of aripiprazole, amisulpride, olanzapine, paliperidone and ziprasidone with a discussion of their therapeutic reference ranges for Chinese patients.

A highly feasible and reliable ultra-high performance liquid chromatography tandem mass spectrometry method was presented for therapeutic drug monitoring of five anti-schizophrenic drugs (amisulpride, olanzapine, aripiprazole, paliperidone and ziprasidone) simultaneously. To meet the requirements of practical clinical usage (easy handling, high throughput and cost effectiveness), the pretreatment process was simplified (only including protein precipitation and mobile phase dilution steps) and the UPLC separation cycle was set within 6 min. The whole methodology was carefully validated according to the latest international guidelines showing the excellent selectivity, accuracy, precision, applicability and stability. After a 10 month clinical application, a retrospective analysis of 253 positive samples was carried out to investigate conformance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie therapeutic reference range for Chinese patients. The results suggested good consistency for olanzapine, aripiprazole, paliperidone and ziprasidone, while for amisulpride, the plasma concentration level (445.2 ± 231.5 ng/mL) was relatively higher than the recommended range (100-320 ng/mL). We supposed that such phenomenon indicated the necessity of reconstructing a Chinese-specific therapeutic reference range for amisulpride treatment, which would be helpful to improve medication efficiency and safety for Chinese patients.

Wang ST ，Li Y 《-》