LC-MS/MS method for simultaneous analysis of uracil, 5,6-dihydrouracil, 5-fluorouracil and 5-fluoro-5,6-dihydrouracil in human plasma for therapeutic drug monitoring and toxicity prediction in cancer patients

2012 ◽  
Vol 27 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Barbara Büchel ◽  
Peter Rhyn ◽  
Stefan Schürch ◽  
Claudia Bühr ◽  
Ursula Amstutz ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Cancer Patients ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Simultaneous Analysis ◽  
Therapeutic Drug ◽  
Toxicity Prediction

scholarly journals Development of a Robust UPLC Method for Simultaneous Determination of a Novel Combination of Sofosbuvir and Daclatasvir in Human Plasma: Clinical Application to Therapeutic Drug Monitoring

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Naser F. Al-Tannak ◽  
Ahmed Hemdan ◽  
Maya S. Eissa
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Chromatographic Method ◽  
Internal Standard ◽  
Oral Intake ◽  
Simultaneous Analysis ◽  
New Combination ◽  
Therapeutic Drug ◽  
Phase System

A rapid and selective UPLC-DAD method was developed and validated for simultaneous analysis of the novel two-drug combination Darvoni® for the treatment of HCV: Sofosbuvir (SF)/Daclatasvir (DC) in human plasma using Ledipasvir as internal standard (IS) where the extraction process was conducted using automated SPE. Although the analysis of the combination after concomitant oral intake of two tablets of SF and DC individually was reported in literature, yet simultaneous analysis of this new combination in human plasma after a single oral dose was not previously reported. The adopted chromatographic separation was achieved on Waters® Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) as a stationary phase using isocratic elution using a mobile phase system of ammonium formate (pH 3.5; 5 mM) and acetonitrile (60:40 v/v) pumped at a flow rate of 0.2 mL.min−1. The UV detection was carried out at 261 nm for SF and 318 nm for DC and IS. SF was eluted at 1.123 min while DC was eluted at 3.179 min. The proposed chromatographic method was validated in accordance with guidelines of FDA for bioanalytical method validation. A linear range was achieved in the range of 25-6400 and 50-12800 ng.mL−1 for SF and DC, respectively. The proposed UPLC-DAD method was found to be accurate with % bias ranging between -10.0-7.2 for SF and -6.9-8.0 for DC. Also it was proved to be precise with % CV for intraday precision ranging between 3.8-9.6 for SF and 2.8-9.2 for DC whereas interday precision ranged between 5.1-9.3 for SF and 3.7-9.1 for DC. Moreover, % extraction recovery ranged between 90.0-107.2 for SF and 93.1-108.0 for DC using the suggested method. The adopted chromatographic method was successfully applied to the therapeutic drug monitoring of SF and DC in healthy volunteers after the oral intake of one Darvoni® tablet.

Importance of voriconazole therapeutic drug monitoring in pediatric cancer patients with invasive aspergillosis

2012 ◽  
Vol 60 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Soo-Han Choi ◽  
Soo-Youn Lee ◽  
Ji-Young Hwang ◽  
Soo Hyun Lee ◽  
Keon Hee Yoo ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Invasive Aspergillosis ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Pediatric Cancer Patients

scholarly journals Development and validation of a new HPLC method for valproic acid determination in human plasma and its application to a therapeutic drug monitoring study

2020 ◽  
Vol 66 (1) ◽  
Author(s):  
Emrah Dural ◽  
Seniha Çelebi ◽  
Aslı Bolayır ◽  
Burhanettin Çiğdem
Keyword(s):  
Valproic Acid ◽  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
High Performance ◽  
High Standard ◽  
Hplc Method ◽  
Therapeutic Drug ◽  
Recommended Treatment ◽  
Monitoring Study

The aim of this study was to develop a new, simple and reliable high performance liquid chromatography (HPLC) method for analysis of valproic acid (VPA) in human plasma and apply to it to a therapeutic drug monitoring study. Also, the relationship between plasma-VPA concentrations and the amount of VPA used by patients was aimed to be evaluated. Plasma samples (0.25 mL) were precipitated with the same volume of acetonitrile and after centrifugation, aliquots were applied to a C18 column (250 mm x 4.6 mm). Mobile phase was prepared with phosphate buffer and acetonitrile (47.5:52.5, v/v). The flow-rate was 1.2 mL/min. Accuracy was between -2.9 and 3.2% and precision was ≤6.6%. Method was specific and sensitive with a detection limit of 2.2 µg/mL and the average recovery was 94.3%. Calibration curve was linear (r2>0.9968) from 10 to 150 µg/mL. Plasma-VPA levels of the epileptic patient population (n=33) treated with VPA between 0.5 and 1.5 g/day were also determined. Patient plasma-VPA concentrations ranged from 2.9 to 166.4 µg/g/mL (56.3±38.8). High RSD% (68.8%) was observed in dose-rated plasma-VPA results. Moreover, VPA plasma levels were found to be outside the recommended treatment range in 30.3% of the patients examined. The procedure described was found to be relatively simple, precise, and applicable for routine therapeutic drug monitoring (TDM) especially in neurology clinics or in toxicology reference laboratories. The high standard deviation (SD) observed in the dose depended plasma-VPA values of the volunteers proved the importance of TDM during the use of this drug. The results showed that for rational drug use, it is important to identify individual polymorphisms in the CYP2C9, CYP2A6 and CYP2B6 subtypes responsible for VPA metabolism, and to rearrange drug doses taking these enzyme activities into account.

scholarly journals Simultaneous Quantification of Methotrexate and Its Metabolite 7-Hydroxy-Methotrexate in Human Plasma for Therapeutic Drug Monitoring

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xinxin Ren ◽  
Zhipeng Wang ◽  
Yunlei Yun ◽  
Guangyi Meng ◽  
Xialan Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Therapeutic Drug ◽  
Tandem Mass ◽  
The Matrix ◽  
Analytical Time

Objective. To establish and validate a simple, sensitive, and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of methotrexate (MTX) and its major metabolite 7-hydroxy-methotrexate (7-OH-MTX) in human plasma. Method. The chromatographic separation was achieved on a Zorbax C18 column (3.5 μm, 2.1 × 100 mm) using a gradient elution with methanol (phase B) and 0.2% formic acid aqueous solution (phase A). The flow rate was 0.3 mL/min with analytical time of 3.5 min. Mass spectrometry detection was performed in a triple-quadruple tandem mass spectrometer under positive ion mode with the following mass transitions: m/z 455.1/308.1 for MTX, 471.0/324.1 for 7-OH-MTX, and 458.2/311.1 for internal standard. The pretreatment procedure was optimized with dilution after one-step protein precipitation. Results. The calibration range of methotrexate and 7-OH-MTX was 5.0-10000.0 ng/mL. The intraday and interday precision and accuracy were less than 15% and within ±15% for both analytes. The recovery for MTX and 7-OH-MTX was more than 90% and the matrix effect ranged from 97.90% to 117.60%. Conclusion. The method was successfully developed and applied to the routine therapeutic drug monitoring of MTX and 7-OH-MTX in human plasma.

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