scholarly journals REGEN-COV® antibody cocktail bioanalytical strategy: comparison of LC-MRM-MS and immunoassay methods for drug quantification

Bioanalysis ◽  
2021 ◽  
Author(s):  
Susan C Irvin ◽  
Samit Ganguly ◽  
Rachel Weiss ◽  
Chinnasamy Elango ◽  
Xuefei Zhong ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Multiple Reaction Monitoring ◽  
Pharmacokinetic Data ◽  
Sample Analysis ◽  
Concentration Data ◽  
Phase Study ◽  
The Usa ◽  
Linear Correlations ◽  
Antibody Cocktail

Aim: In response to the COVID-19 pandemic, Regeneron developed the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV® (RONAPREVE® outside the USA). Drug concentration data was important for determination of dose, so a two-part bioanalytical strategy was implemented to ensure the therapy was rapidly available for use. Results & methodology: Initially, a liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay, was used to analyze early-phase study samples. Subsequently, a validated electrochemiluminescence (ECL) immunoassay was implemented for high throughput sample analysis for all samples. A comparison of drug concentration data from the methods was performed which identified strong linear correlations and for Bland-Altman, small bias. In addition, pharmacokinetic data from both methods produced similar profiles and parameters. Discussion & conclusion: This novel bioanalytical strategy successfully supported swift development of a critical targeted therapy during the COVID-19 public health emergency.

scholarly journals Simultaneous determination of ginkgolide A, B, C, bilobalide and rutin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study

2021 ◽  
Author(s):  
Bingying Hu ◽  
Yingying Sun ◽  
Min Wang ◽  
Zhisheng He ◽  
Shanshan Chen ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Half Life ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Flavonol Glycoside ◽  
Pharmacokinetic Data ◽  
Good Precision ◽  
Ginkgolide A ◽  
Terminal Half Life

Abstract A reliable LC-MS/MS method for the determination of five bioactive constituents (bilobalide, BLL; ginkgolide A, GLA; ginkgolide B, GLB; ginkgolide C, GLC; rutin) of Ginkgo biloba leaf extracts (GBE) in rat plasma was established, fully validated and applied to an intragastric pharmacokinetic study of a preparation of GBE in rat. Samples were extracted with ethyl acetate. C18 column was selected as analytical column in this method. Mobile phase was water with 0.01% formic acid and acetonitrile. Quantification was performed in negative multiple-reaction monitoring mode. Matrix instability of terpene lactones was noticed and hydrochloric acid was used as a stabilizer. This method showed good precision and accuracy, recovery was reproducible and matrix effect was negligible. Among four terpene lactones, BLL had the highest exposure and the shortest terminal half-life, GLA and GLB had lower exposure and longer terminal half-life, the exposure of GLC was lowest and its terminal half-life was the maximum, and all of them showed rapid absorption. This study provides a reference for determination of terpene lactones and flavonol glycoside prototypes in GBE and offers pharmacokinetic data of flavonol glycoside prototype in GBE.

Simultaneous Determination of Eight Potential Q-Markers in Zishen Tongguan Capsules Based on UHPLC-MS/MS

2020 ◽  
Vol 17 (1) ◽  
pp. 47-56
Author(s):  
Shun Liu ◽  
Xun Wang ◽  
Kaiping Zou ◽  
Wei Liu ◽  
Cunyu Li ◽  
...  
Keyword(s):  
Quality Control ◽  
Chinese Medicine ◽  
Simultaneous Determination ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Quality Markers ◽  
High Repeatability ◽  
Comprehensive Study

Background: Zishen Tongguan (ZSTG) capsules were prepared at the Affiliated Hospital of Nanjing University of Chinese Medicine and have been proven to be clinically effective for treating pyelonephritis and benign prostatic hyperplasia. However, the quality standards are not ideal; a comprehensive study of the “quality markers” (Q-markers), the chemicals inherent in traditional Chinese medicine and its preparations, has not been carried out. Experimental Methods: In this paper, a sensitive and specific ultra-high-performance liquid chromatographictandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of eight potential Q-markers of ZSTG, including timosaponin A3, berberine, jatrorrhizine, phellodendrine, palmatine, mangiferin, neomangiferin, and timosaponin BII. A Kromasil 100-3.5 C18 column was used with a mobile phase of 0.2% formic acid with acetonitrile, and gradient elution at a flow rate of 0.2 mL/min was achieved in 13 minutes and used for separation. Detection was performed in positive/negative mode with multiple reaction monitoring (MRM). Results: The analytical method was validated in terms of the sensitivity, linearity, accuracy, precision, repeatability, stability and recovery. The method established here was successfully applied to study the potential Q-markers in 8 batches of commercial samples, which demonstrated its use in improving the quality control of ZSTG. Conclusion: The developed method had high repeatability and accuracy and was suitable for the simultaneous analysis of multiple Q-markers, which may provide a new basis for the comprehensive assessment and overall quality control of ZSTG.

Sampling, Preservation and Counting of Samples II: Zooplankton

2017 ◽  
Author(s):  
Peter H. Wiebe ◽  
Ann Bucklin ◽  
Mark Benfield
Keyword(s):  
Genetic Analysis ◽  
High Speed ◽  
Morphological Analysis ◽  
Taxonomic Composition ◽  
Sampling Techniques ◽  
Sample Analysis ◽  
Sample Preservation ◽  
The Past ◽  
Plankton Collection

This chapter reviews traditional and new zooplankton sampling techniques, sample preservation, and sample analysis, and provides the sources where in-depth discussion of these topics is addressed. The net systems that have been developed over the past 100+ years, many of which are still in use today, can be categorized into eight groups: non-opening/closing nets, simple opening/closing nets, high-speed samplers, neuston samplers, planktobenthos plankton nets, closing cod-end samplers, multiple net systems, and moored plankton collection systems. Methods of sample preservation include preservation for sample enumeration and taxonomic morphological analysis, and preservation of samples for genetic analysis. Methods of analysis of zooplankton samples include determination of biomass, taxonomic composition, and size by traditional methods; and genetic analysis of zooplankton samples.

Rhetorical moves in political discourse: closing statements by presidential candidates in US primary election debates

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Schubert
Keyword(s):  
Political Discourse ◽  
Political Agenda ◽  
Election Campaigns ◽  
Sample Analysis ◽  
Presidential Candidates ◽  
Primary Election ◽  
Presidential Primary ◽  
The Usa ◽  
Discourse Studies ◽  
Political Persuasion

Abstract Presidential primary debates in the USA are commonly concluded by brief closing statements, in which the competitors outline the central messages of their election campaigns. These statements constitute a subgenre characterized by a set of recurring rhetorical moves, which are defined as functional units geared towards the respective communicative objective, in this case political persuasion. Located at the interface of rhetorical move analysis and political discourse studies, this paper demonstrates that moves and embedded steps in closing statements fulfill the persuasive function of legitimizing the respective candidate as the most preferable presidential successor. The study is based on the transcripts of 98 closing statements, which were extracted from eight Democratic and eleven Republican primary debates held between August 2015 and April 2016. Typical moves, such as projecting the speaker’s future political agenda or diagnosing the current situation in America, are presented with the help of illustrative examples, frequencies of occurrence, and a sample analysis of a complete closing statement.

scholarly journals Advances in LC–MS/MS Methods for Allergen Testing, Meat Speciation, and Gelatin Speciation

2019 ◽  
Vol 102 (5) ◽  
pp. 1309-1315
Author(s):  
Jianru Stahl-Zeng ◽  
Ashley Sage ◽  
Philip Taylor ◽  
Jeremy Dietrich Netto ◽  
Tuo Zhang
Keyword(s):  
Mass Spectrometer ◽  
Multiple Reaction Monitoring ◽  
Proteome Analysis ◽  
Food Product ◽  
Transition Analysis ◽  
Tandem Quadrupole Mass Spectrometer ◽  
Signature Peptides ◽  
Unique Markers ◽  
Multiple Species

Abstract Background: Food authenticity is demanded by the consumer at all times. The consumer places trust in the manufacturer that the food product is genuine in terms of what is recorded on the packaging label. Objective: Recent advancements in LC–tandem MS methodology in the detection of allergens, meat, and gelatin speciation in raw food products and processed foods are detailed in this paper. Method: For each of the three methods, initial proteome analysis and the screening leading to the determination of unique tryptic peptides were conducted using a high-resolution, accurate tandem mass spectrometer. Having identified the unique markers, the method was transferred to a tandem quadrupole mass spectrometer for a higher-sensitivity quantitative study, multiple reaction monitoring transition analysis. Results: For the allergens method a detection limit of at least 10 ppm was attained across the 12 allergen peptides in this workflow. In the gluten workflow the resulting chromatograms show good detection down to 5 ppm, with no interference from the food matrices. The meat speciation method details that signature peptides could be readily identified at 1% w/w with no matrix interference. Conclusions: These single-injection workflows with cycle-time optimization enable wide coverage of analytes to identify multiple species within challenging matrix samples.

scholarly journals A “Smart” Biosensor-Enabled Intravascular Catheter and Platform for Dynamic Delivery of Propofol to “Close the Loop” for Total Intravenous Anesthesia

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 370-377
Author(s):  
Edward Chaum ◽  
Ernő Lindner
Keyword(s):  
Real Time ◽  
Drug Distribution ◽  
Population Based ◽  
Pharmacokinetic Data ◽  
Drug Infusion ◽  
Blood Concentrations ◽  
The Usa ◽  
The Difference ◽  
Automated Delivery

ABSTRACT Background Target-controlled infusion anesthesia is used worldwide to provide user-defined, stable, blood concentrations of propofol for sedation and anesthesia. The drug infusion is controlled by a microprocessor that uses population-based pharmacokinetic data and patient biometrics to estimate the required infusion rate to replace losses from the blood compartment due to drug distribution and metabolism. The objective of the research was to develop and validate a method to detect and quantify propofol levels in the blood, to improve the safety of propofol use, and to demonstrate a pathway for regulatory approval for its use in the USA. Methods We conceptualized and prototyped a novel “smart” biosensor-enabled intravenous catheter capable of quantifying propofol at physiologic levels in the blood, in real time. The clinical embodiment of the platform is comprised of a “smart” biosensor-enabled catheter prototype, a signal generation/detection readout display, and a driving electronics software. The biosensor was validated in vitro using a variety of electrochemical methods in both static and flow systems with biofluids, including blood. Results We present data demonstrating the experimental detection and quantification of propofol at sub-micromolar concentrations using this biosensor and method. Detection of the drug is rapid and stable with negligible biofouling due to the sensor coating. It shows a linear correlation with mass spectroscopy methods. An intuitive graphical user interface was developed to: (1) detect and quantify the propofol sensor signal, (2) determine the difference between targeted and actual propofol concentration, (3) communicate the variance in real time, and (4) use the output of the controller to drive drug delivery from an in-line syringe pump. The automated delivery and maintenance of propofol levels was demonstrated in a modeled benchtop “patient” applying the known pharmacokinetics of the drug using published algorithms. Conclusions We present a proof-of-concept and in vitro validation of accurate electrochemical quantification of propofol directly from the blood and the design and prototyping of a “smart,” indwelling, biosensor-enabled catheter and demonstrate feedback hardware and software architecture permitting accurate measurement of propofol in blood in real time. The controller platform is shown to permit autonomous, “closed-loop” delivery of the drug and maintenance of user-defined propofol levels in a dynamic flow model.

LC–MS–MS Analysis of Mirtazapine in Plasma, and Determination of Pharmacokinetic Data for Rats

2008 ◽  
Vol 68 (1-2) ◽  
pp. 65-70 ◽  
Author(s):  
Xiao Hong ◽  
Yao Yao ◽  
Shen Hong ◽  
Chen Lei
Keyword(s):  
Pharmacokinetic Data ◽  
Ms Analysis

HPLC/Tandem Mass Spectrometric Studies on Steroidal Saponins: An Example of Quantitative Determination of Shatavarin IV from Dietary Supplements Containing Asparagus racemosus

2014 ◽  
Vol 97 (6) ◽  
pp. 1497-1502 ◽  
Author(s):  
Dada Patil ◽  
Manish Gautam ◽  
Sunil Gairola ◽  
Suresh Jadhav ◽  
Bhushan Patwardhan
Keyword(s):  
Acetic Acid ◽  
Dietary Supplements ◽  
Quantitative Estimation ◽  
Multiple Reaction Monitoring ◽  
Asparagus Racemosus ◽  
Steroidal Saponin ◽  
Esi Ms ◽  
Tandem Mass Spectrometric ◽  
Positive Ion

Abstract Asparagus racemosus (AR) is a popular botanical present in several Ayurvedic medicines and nutritional and dietary supplements with immunomodulatory, galactogogue, and anticancer activity. A steroidal saponin known as shatavarin IV is one of the active constituents of AR. A new, selective, and rapid HPLC/MS/MS method has been developed and validated for quantitative estimation of shatavarin IV in crude, processed, and marketed samples of AR. The analytes were separated on a Luna C18 column using simple isocratic elution with water (0.1% acetic acid)–acetonitrile (0.1% acetic acid; 70 + 30, v/v) at a flow rate of 0.8 mL/min. The analytes were detected by electrospray ionization (ESI)-MS/MS and quantified using multiple reaction monitoring techniques in the positive ion mode. The method showed excellent linearity (r2 > 0.998) over the concentration range of 7.5 to 254 ng/mL with LOD of 2.5 ng/mL. Precision (RSD) and accuracy (recovery) were found in the ranges of 2.00 to 5.15 and 102 to 110%, respectively. The validated HPLC/ESI-MS/MS method was successfully applied to the quantification of shatavarin IV in crude, processed, and marketed (single or multiherb) AR samples. Therefore, this method could be used for QC and standardization of pharmaceutical or nutritional products containing AR.

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