scholarly journals UPLC-MS/MS Method for Simultaneous Determination of 14 Antimicrobials in Human Plasma and Cerebrospinal Fluid: Application to Therapeutic Drug Monitoring

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Huiting Sun ◽  
Han Xing ◽  
Xueke Tian ◽  
Xiaojian Zhang ◽  
Jing Yang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Therapeutic Drug Monitoring ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Quantitative Methods ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Therapeutic Drug ◽  
Limit Of Quantification ◽  
Acquity Uplc

Pharmacokinetics/pharmacodynamics is the foundation for guiding the rational application of antibiotics in clinical practice, so it is necessary to establish quantitative methods for accurate drug concentration determination. This study aimed to develop a rapid and simple ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of 14 antibiotics (amikacin, etimicin, ceftazidime, cefepime, cefoperazone, ceftriaxone, daptomycin, latamoxef, linezolid, meropenem, biapenem, ampicillin, norvancomycin, and vancomycin) in human plasma and cerebrospinal fluid. Antibiotics were chromatographically separated on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) via gradient elution within 3 minutes and were monitored using positive ion fitted with multiple reaction monitoring. The lower limit of quantification was 0.05–2.0 μg·mL−1. The method was verified according to the FDA bioanalysis method validation guidelines, which showed excellent accuracy (from 86.75% to 110.85%) and precision (from 0.46% to 10.97%). At last, this method was successfully applied to therapeutic drug monitoring in 113 patients under antibiotics treatment.

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.

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

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.

scholarly journals Rapid liquid chromatography tandem mass spectrometry determination of rivaroxaban levels in human plasma for therapeutic drug monitoring

2017 ◽  
Vol 25 (2) ◽  
Author(s):  
Andreea Varga ◽  
Răzvan Constantin Șerban ◽  
Daniela Lucia Muntean ◽  
Cristina Maria Tătar ◽  
Lenard Farczadi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Tandem Mass Spectrometry ◽  
Human Plasma ◽  
Drug Monitoring ◽  
Single Step ◽  
Therapeutic Drug ◽  
Tandem Mass ◽  
Limit Of Quantification

AbstractA rapid, sensitive, high-throughput liquid chromatography coupled with tandem mass spectrometry method for the quantification of rivaroxaban from human plasma has been developed and validated. For the analytical separation a Zorbax SB-C18 column with isocratic flow of mobile phase composed of 0.2% formic acid in water and acetonitril (65:35, V/V) with a flow rate of 1 mL/min at a temperature of 45ºC was used. Detection of rivaroxaban was performed using positive electrospray ionization and MS/MS mode (sum of m/z 231.1; 289.2 and 318.2 from m/z 436.3). Plasma samples were prepared using single-step protein precipitation with methanol. Method validation was performed with regards to selectivity, linearity (r >0.9927), within-run and between-run precision (CV< 13.1 %) and accuracy (bias< 9.4 %) over a concentration range of 24.00 - 960.00 ng/mL plasma. Recovery was between 96.5 - 108.5% and the lower limit of quantification of rivaroxaban was 24.00 ng/mL. The developed method is simple, rapid, and selective, requires small plasma sample volumes, and was successfully applied for therapeutic drug monitoring of rivaroxaban in treated patients.

Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole

2017 ◽  
Vol 54 (6) ◽  
pp. 686-695 ◽  
Author(s):  
John M Wadsworth ◽  
Anna M Milan ◽  
James Anson ◽  
Andrew S Davison
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Turnaround Time ◽  
Therapeutic Drug ◽  
Tandem Mass ◽  
Lower Limits

Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20  µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3  µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R2 = 0.995) and 5 mg/L for posaconazole (R2 = 0.990) and itraconazole (R2 = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring.

scholarly journals Determination of sarecycline by UPLC-MS/MS and its application to pharmacokinetic study in rats

2020 ◽  
Author(s):  
Yonghui Shen ◽  
Deru Meng ◽  
Feifei Chen ◽  
Hui Jiang ◽  
Liming Hu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Chronic Inflammatory Disease ◽  
Linear Calibration ◽  
Limit Of Quantification ◽  
Acquity Uplc ◽  
Intravenous And Oral Administration

AbstractSarecycline is a narrow-spectrum antibiotic for the treatment of acne, which is a chronic inflammatory disease of the hair follicle sebaceous glands. In the study, UPLC-MS/MS was used to establish a rapid and accurate analytical method. The sarecycline was determined with poziotinib as internal standard (IS) in rat plasma. An ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) could performe chromatographic separation with the mobile phase (methanol: water of 0.1% formic acid) with gradient elution. The ions of target fragment were m/z 488.19→410.14 for sarecycline and m/z 492.06→354.55 for poziotinib, which could quantify the electrospray ionization of positive multiple reaction monitoring (MRM) mode. The linear calibration curve of the concentration range was 1–1,000 ng/mL for sarecycline with a lower limit of quantification (LLOQ) of 1 ng/mL. The mean recovery was between 82.46 and 95.85% for sarecycline and poziotinib in rat plasma. RSD for precision of inter-day and intra-day were between 3.24 and 13.36%, and the accuracy ranged from 105.26 to 109.75%. The developed and validated method was perfectly used in the pharmacokinetic study and bioavailability of sarecycline after intravenous and oral administration in rats.

Therapeutic drug monitoring of linezolid: HPLC-based assays for routine quantification of linezolid in human serum and cerebrospinal fluid

2022 ◽  
pp. ejhpharm-2021-003036
Author(s):  
Stefan Günther ◽  
Andreas Reimer ◽  
Horst Vogl ◽  
Stephan Spenke ◽  
Hanns-Christian Dinges ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Therapeutic Drug Monitoring ◽  
Human Serum ◽  
Drug Monitoring ◽  
Therapeutic Drug

scholarly journals Routine clinical monitoring of sirolimus (rapamycin) whole-blood concentrations by HPLC with ultraviolet detection

1996 ◽  
Vol 42 (12) ◽  
pp. 1943-1948 ◽  
Author(s):  
K L Napoli ◽  
B D Kahan
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Clinical Status ◽  
Reversed Phase ◽  
Therapeutic Drug ◽  
Full Time ◽  
Limit Of Quantification ◽  
Blood Concentrations ◽  
Ultraviolet Detection

Abstract During phase I/II clinical trials of sirolimus (rapamycin; SRL), therapeutic drug monitoring was performed with a multistep liquid-liquid extraction of 1-mL aliquots of whole blood followed by reversed-phase HPLC with ultraviolet detection. Blood was sampled according to a standardized protocol and clinical status. SRL concentrations were interpolated from calibration curves with a linear range of 0-50 micrograms/L and 1 microgram/L lower limit of quantification. Quality control was monitored over 68 consecutive analytical runs by using frozen aliquots of SRL-supplemented pooled whole blood at 4, 12, and 32 micrograms/L. These samples showed mean concentrations of 3.7 +/- 0.6, 10.9 +/- 1.1, and 29.6 +/- 2.6 micrograms/L, respectively. This method for therapeutic drug monitoring of SRL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time. With this method, a strong linear relation (r2 = 0.946, Sy/x = 0.41, n = 115) between the average SRL concentration over a 24-h period and the SRL concentration at the 24th h was revealed.

Sign in / Sign up

Export Citation Format

Share Document