LC–MS/MS quantification of ataluren and ataluren acyl glucuronide in human plasma/urine: application in clinical studies

Bioanalysis ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 1545-1555
Author(s):  
Diksha Kaushik ◽  
Jiyuan Ma ◽  
Guodong Gu ◽  
Seongwoo Hwang ◽  
Young-Choon Moon ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Human Plasma ◽  
Acyl Migration ◽  
Successful Completion ◽  
Quantification Method ◽  
Acyl Glucuronide ◽  
Pharmacokinetic Assessment ◽  
Plasma And Urine Samples ◽  
First Time ◽  
Direct Quantification

Background: This paper describes for the first-time analytical procedures established to resolve the challenges associated with simultaneous and direct quantification of ataluren and ataluren- O-1β-acyl glucuronide (AAG) by LC–MS/MS in human plasma and urine matrices. Methodology/results: The plasma quantification method was validated for calibration range of 12.5–12500 ng/ml for ataluren and 6.25–2500 ng/ml for AAG. The urine quantification method was validated for calibration range of 0.01–10 and 1–1000 μg/ml for ataluren and AAG, respectively. Plasma and urine samples were stabilized upon collection and through storage to prevent hydrolysis and acyl migration of AAG. Conclusion: Methods described in this paper enabled successful completion of ataluren clinical pharmacology studies for simultaneous pharmacokinetic assessment of ataluren and AAG.

scholarly journals Analysis of Pembrolizumab in Human Plasma by LC-MS/HRMS. Method Validation and Comparison with Elisa

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 621
Author(s):  
Aurélien Millet ◽  
Nihel Khoudour ◽  
Jérôme Guitton ◽  
Dorothée Lebert ◽  
François Goldwasser ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Plasma ◽  
High Resolution Mass Spectrometry ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Limit Of Quantification ◽  
Immunoglobulin G4 ◽  
Positive Mode ◽  
Surrogate Peptide ◽  
First Time

Pembrolizumab is a humanized immunoglobulin G4-kappa anti-PD1 antibody used in the treatment of different solid tumors or haematological malignancies. A liquid chromatography coupled with a high resolution mass spectrometry (orbitrap technology) method was fully developed, optimized, and validated for quantitative analysis of pembrolizumab in human plasma. A mass spectrometry assay was used for the first time a full-length stable isotope-labelled pembrolizumab-like (Arginine 13C6-15N4 and Lysine 13C6-15N2) as an internal standard; the sample preparation was based on albumin depletion and trypsin digestion and, finally, one surrogate peptide was quantified in positive mode. The assay showed good linearity over the range of 1–100 μg/mL, a limit of quantification at 1 μg/mL, excellent accuracy from 4.4% to 5.1%, and also a between-day precision below 20% at the limit of quantification. In parallel, an in-house ELISA was developed with a linearity range from 2.5 to 50 µg/mL. Then, results were obtained from 70 plasma samples of cancer patients that were treated with pembrolizumab and quantified with both methods were compared using the Passing-Bablok regression analysis and Bland-Altman plotting. The LC-MS/HRMS method is easy to implement in the laboratory for use in the context of PK/PD studies, clinical trials, or therapeutic drug monitoring.

Pharmacokinetic assessment of immunosuppressive activity of antibiotics in human plasma by a modification of the mixed lymphocyte reaction

1984 ◽  
Vol 12 (6) ◽  
pp. 483-485 ◽  
Author(s):  
CLAUDIO DE SIMONE ◽  
L. PUGNALONI ◽  
A. CILLI ◽  
E. M. A. FORASTIERI ◽  
B. BERNARDINI ◽  
...  
Keyword(s):  
Human Plasma ◽  
Mixed Lymphocyte Reaction ◽  
Immunosuppressive Activity ◽  
Pharmacokinetic Assessment

Dispersive suspended-solidified floating organic droplet microextraction of nonsteroidal anti-inflammatory drugs: comparison of suspended droplet-based and dispersive-based liquid-phase microextraction methods

RSC Advances ◽  
2015 ◽  
Vol 5 (129) ◽  
pp. 106574-106588 ◽  
Author(s):  
Behruz Barfi ◽  
Alireza Asghari ◽  
Maryam Rajabi ◽  
Nasim Mirkhani
Keyword(s):  
Liquid Phase ◽  
Human Plasma ◽  
Urine Samples ◽  
Liquid Phase Microextraction ◽  
Human Plasma And Urine ◽  
Plasma And Urine Samples ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Suspended Droplet

A dispersive suspended-solidified floating organic droplet microextraction method was developed for determination of some nonsteroidal anti-inflammatory drugs in human plasma and urine samples.

Quantitation of ivosidenib in human plasma via LC–MS/MS and its application in clinical trials

Bioanalysis ◽  
2021 ◽  
Author(s):  
Feng Yin ◽  
Shaoxia Yu ◽  
Rohini Narayanaswamy ◽  
Heidi Mangus ◽  
Erin McCourt ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Human Plasma ◽  
Internal Standard ◽  
Clinical Samples ◽  
Isocitrate Dehydrogenase 1 ◽  
Bioanalytical Method ◽  
Molecule Inhibitor ◽  
Chiral Lc ◽  
First Time

Aim: Ivosidenib is a potent and selective small molecule inhibitor of mutant isocitrate dehydrogenase 1. Accurate measurement of ivosidenib is the key to ivosidenib pharmacokinetics in clinical trials. Materials & methods: Quantitation of ivosidenib was conducted by using a stable isotope labeled compound (ivosidenib-d4) as the internal standard. Results: This assay was validated and successfully applied to support multiple clinical trials. Selected clinical samples were also tested by a chiral LC–MS/MS method against four ivosidenib isomer standards to exclude the possibility of in vivo racemization of ivosidenib. Conclusion: A robust LC–MS/MS method was validated for ivosidenib in human plasma. This is the first time for ivosidenib bioanalytical method in any human matrix to be reported.

scholarly journals Human plasma dynamically quenches the fluorescein at the initial point of oxygen radical absorption capacity (ORAC) assay

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Harshi Gunawardena ◽  
Renuka Silva ◽  
Pathmasiri Ranasinghe
Keyword(s):  
Human Plasma ◽  
Fluorescence Probe ◽  
Initial Point ◽  
Oxygen Radical ◽  
Absorption Capacity ◽  
Peroxyl Radicals ◽  
Dynamic Quenching ◽  
Initial Stage ◽  
First Time ◽  
Dose Dependent

Abstract Objective Oxygen radical absorbance capacity (ORAC) assay measures the quenching of fluorescent probe by peroxyl radicals. Antioxidants present in biological systems block the quenching of fluorescence probe. We experienced the dynamic quenching of fluorescein, the fluorescence probe used in ORAC assay by the human plasma while plasma ORAC assay was optimized. Therefore, for the first time, we report the quenching of fluorescein by human plasma at the initial point of ORAC assay. Results Aqueous whole and non-protein fractions of plasma were used in the analysis. Since the both fractions showed a similar pattern of quenching at the initial stage, quenched percentage of fluorescein was calculated and added to each sample in subsequent analysis. Addition of extra 20% fluorescein allowed plasma samples to quench the required amount of fluorescein and follow the normal decay curves afterwards. Further, change of fluorescein quenching (ΔF/F0) disclosed a dose dependent linear relationship with plasma (R2 = 0.8). It can be speculated that dynamic quenching exhibited by human plasma biomolecule/s at the initial stage would be of non-protein aqueous phase molecule/s. We suggest initiating further studies to detect, identify and quantify the fluorescein quenching biomolecules present in human plasma for further improvements in plasma ORAC assay.

scholarly journals Sensitive Analysis of Idarubicin in Human Urine and Plasma by Liquid Chromatography with Fluorescence Detection: An Application in Drug Monitoring

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5799
Author(s):  
Olga Maliszewska ◽  
Natalia Treder ◽  
IIona Olędzka ◽  
Piotr Kowalski ◽  
Natalia Miękus ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Human Plasma ◽  
Fluorescence Detection ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Biological Fluids ◽  
Internal Standard ◽  
Urine Samples ◽  
Human Plasma And Urine ◽  
Plasma And Urine Samples

A new approach for the sensitive, robust and rapid determination of idarubicin (IDA) in human plasma and urine samples based on liquid chromatography with fluorescence detection (LC-FL) was developed. Satisfactory chromatographic separation of the analyte after solid-phase extraction (SPE) was performed on a Discovery HS C18 analytical column using a mixture of acetonitrile and 0.1% formic acid in water as the mobile phase in isocratic mode. IDA and daunorubicin hydrochloride used as an internal standard (I.S.) were monitored at the excitation and emission wavelengths of 487 and 547 nm, respectively. The method was validated according to the FDA and ICH guidelines. The linearity was confirmed in the range of 0.1–50 ng/mL and 0.25–200 ng/mL, while the limit of detection (LOD) was 0.05 and 0.125 ng/mL in plasma and urine samples, respectively. The developed LC-FL method was successfully applied for drug determinations in human plasma and urine after oral administration of IDA at a dose of 10 mg to a patient with highly advanced alveolar rhabdomyosarcoma (RMA). Moreover, the potential exposure to IDA present in both fluids for healthcare workers and the caregivers of patients has been evaluated. The present LC-FL method can be a useful tool in pharmacokinetic and clinical investigations, in the monitoring of chemotherapy containing IDA, as well as for sensitive and reliable IDA quantitation in biological fluids.

Sign in / Sign up

Export Citation Format

Share Document