A simple isotope-labeled UHPLC–MS/MS assay for simultaneous quantification of methotrexate, imatinib and dasatinib

Aim: To assist therapeutic dose adjustment in clinic, a reliable concentration measurement is quite necessary for therapeutic drug monitoring. Results: A UHPLC–MS/MS bioassay for simultaneous determination of methotrexate, imatinib and dasatinib using isotope dilution internal standardization has been established and fully validated as per China Food and Drug Administration guideline. After a simple protein precipitation, the analytes were separated by a gradient elution within 3 min and mass detection was performed via ESI+ mode with SRM. The calibration curves were in the range of 5–100 ng/ml for methotrexate, 25–5000 ng/ml for imatinib and 1–250 ng/ml for dasatinib. Imprecision and inaccuracy values were ≤9.44% and ≤12.81% for all analytes, respectively. Conclusion: The developed method is appropriate for therapeutic drug monitoring, being applied to help individualized therapy in patients with acute lymphoblastic leukemia.

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LC-MS for Simultaneous Determination of Vancomycin and Teicoplanin in Patient Plasma and its Application to Therapeutic Drug Monitoring

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180801095208 ◽

2018 ◽

Vol 15 (1) ◽

pp. 95-102

Author(s):

Guiyan Yuan ◽

Danni Liu ◽

Fanlong Bu ◽

Yanyan Wang ◽

Benjie Wang ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Simultaneous Determination ◽

Drug Monitoring ◽

Severe Infection ◽

Gradient Elution ◽

Storage Conditions ◽

Therapeutic Drug ◽

Individual Response ◽

Ionization Source

Background: Therapeutic drug monitoring is recommended for patients taking vancomycin and teicoplanin to ensure pharmaceutical efficacy and prevent toxicity. Only few studies were reported regarding the simultaneous determination of vancomycin and teicoplanin in human plasma. Objective: The study aimed at developing and validating a Liquid Chromatography-Mass Spectrometry (LC-MS) method for simultaneous determination and therapeutic drug monitoring of vancomycin and teicoplanin in patients with severe infection. Method: Plasma was processed by protein precipitation extraction. The analytes were separated on a C18 column by gradient elution with 0.1% formic acid and acetonitrile as mobile phase and measured by electrospray ionization source in positive selective ion monitoring mode at m/z 724.7 (vancomycin), 940.7 (teicoplanin) and 329.0 (bergenin). The plasma samples (104) were obtained from patients who were taking vancomycin or teicoplanin for further analysis. Results: The calibration curves were linear within the range of 0.25–40 µg/mL for vancomycin, and 0.5-40 µg/mL for teicoplanin. Either inter- or intra-day precision was less than 10.01 %. The extraction recoveries ranged from 89.99 to 94.29% for vancomycin and from 39.83 to 40.16 % for teicoplanin. Vancomycin and teicoplanin in plasma were stable at various storage conditions. The measured mean trough concentrations were 12.313 µg/mL for vancomycin and 8.765 µg/mL for teicoplanin. Conclusion: This method was successfully applied to therapeutic drug monitoring of vancomycin and teicoplanin in patients. It is with great clinic value for monitoring and predicting the individual response of patients under treatment.

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A Validated LC-MS/MS Method for the Determination of Mezlocillin in Plasma: an Adapted Method for Therapeutic Drug Monitoring in Children

Current Pharmaceutical Analysis ◽

10.2174/1573412916999200517113525 ◽

2020 ◽

Vol 16 ◽

Author(s):

Bo-Hao Tang ◽

Min Kan ◽

Xin-Mei Yang ◽

Rong-Hua Wang ◽

Hai-Yan Shi ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Trough Concentration ◽

Drug Monitoring ◽

Respiratory Infections ◽

Internal Standard ◽

Gradient Elution ◽

Therapeutic Drug ◽

Limit Of Quantification ◽

Liquid Chromatography Tandem Mass

Background: Mezlocillin is off-label used for the treatment of respiratory infections in children. Therapeutic drug monitoring (TDM) data are also limited in children. A sensitive Liquid chromatography tandem mass spectrometry (LC–MS/MS) method adapted to children was developed and validated for the determination of mezlocillin plasma concentration in present study. Method: Mezlocillin, extracted from a volume of 50 μL plasma using acetonitrile, was analyzed on an online LC–MS/MS system with an Agilent 1290 Infinity UHPLC (Agilent Technologies, CA, USA) coupled to an AB SCIEX QTRAP 6500PLUS MS/MS (AB Sciex, Framingham, MA, USA) with ceftiofur as an internal standard. HPLC separation was performed on a C18 column with ultrapure water and acetonitrile as gradient elution at a flow rate of 0.4 mL/min at 30o C. Analyst TM Version 1.5.2 (Applied Biosystems) was used for data acquisition. The total chromatographic run time was 1.6 min. Results: LC/MS/MS method used for TDM of mezlocillin in children was developed and validated. This assay has a lower limit of quantification of 0.025 μg/mL for mezlocillin with 50 μL plasma. Good linearity was achieved for mezlocillin over the range 0.025 to 20 μg /mL. The acceptance criteria were met in all cases. Among 36 patients aged 0.16-1.63 years old, only one patient had detectable trough concentration higher than 1 μg/mL. Conclusion: LC-MS/MS method with 50 μL plasma developed in our study was successfully applied to TDM of mezlocillin in children. The high variability of trough concentration highlighted TDM is important to optimize mezlocillin therapy in children.

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