Small Molecule Bioanalysis

When searching for the hard-to-find molecule, gaining insights and expertise from the DMPK community is critical. Browse these resources to be even more effective in quantifying small molecules for drug efficacy.

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Comprehending COVID-19: LC-MS/MS Analysis of Small Molecule Anti-Viral and Anti-Inflammatory Drugs in Plasma in Clinical Research
August 2020

A simple and rapid LC-MS/MS method has been developed for the analysis of anti-viral and anti-inflammatory drugs in plasma for clinical research using the ACQUITY UPLC I-Class/Xevo TQ-S micro IVD System.

The method uses a simple protein precipitation to extract the drugs from plasma and chromatography with a CORTECS T3 Column to enable selective and rapid separation of the drugs in the extracted sample. Analytical sensitivity, linearity, precision, and accuracy are excellent with reproducible extraction efficiency and matrix effects.

Clinical research into the impact of these drugs and their metabolites on SARS-CoV-2 is still ongoing. Phosphorylated metabolites of the RNA polymerase inhibitors haven’t been evaluated here and they may be of additional interest, with nucleoside triphosphate of remdesivir representing the predominant metabolite in Peripheral Blood Mononuclear Cells (PBMCs).3 Phosphorylated molecules bind to metals and represent an analytical challenge for robust and reproducible quantification in LC-MS/MS. Chelator additives or the use of high performance surface (HPS) technologies can help bridge the gap in providing a method for robust quantification of phosphorylated molecules in future studies using LC-MS/MS.

QuanOptimize: A Software Tool that Enables Rapid, Consistent, and Accurate MRM Method Development for Large Numbers of Small Molecule Analytes
September 2020

Discovery bioanalytical laboratories routinely develop methods for hundreds of compounds per week to support the various programs in their pipeline. Developing methods for each of these compounds individually can be time-consuming and tedious. Since the approach to small molecule method development is well understood, automation of this process is desirable. QuanOptimize automates the MRM method development for large sets of compounds. It can store the final method parameters to a database, automatically run sample lists using the optimized method, create data processing methods, and generate quantitative result with the click of a single button. QuanOptimize ensures consistent quality of methods across multiple users, reduces sample consumption and saves time by up to 5-fold.

Here, we discuss the use of QuanOptimize to develop methods for a set of 18 small molecule compounds using generic tune page and LC methods.

Development of a Bioanalytical SPE LC-MS/MS Assay for Oligonucleotides
January 2021

Over the past decade, there has been increased research oligonucleotides therapies (ONTs). With improved target specificity of next-generation oligonucleotides, demand for LC-MS bioanalytical assays in support of their research and development has also increased.

Developing robust, sensitive and selective sample preparation and LC-MS methods for ONTs remains quite challenging, due to their size, poly-anionic nature, physiochemical diversity, and stability, which often results in poor sample recovery from biomatrices, poor MS sensitivity due to limited ionization/fragmentation, and resolution from endogenous matrix interferences due to poor RP chromatographic retention.

This work described herein provides a single, simple method for the quantification of various oligonucleotides (15-35mer) from serum, using RP and mixed-mode µElution SPE sample preparation and analytical scale sub-2µm LC. This method achieves high recovery and low matrix effects, while achieving LODs as low as 0.5-1.0 ng/mL extracted from plasma/sera.

CDMO Pushes Bioanalytical Boundaries with Innovative Topical and Transdermal Services

In this case study learn how MedPharm is successful in its innovative approach to topical and transdermal product design and development services by utilizing Waters bioanalytical instrumentation and software solutions.

A Rapid Method for The Ultra-Sensitive Quantification of Fluticasone Propionate and Salmeterol Xinafoate from Human Plasma

This high-throughput method achieves the lowest published LLOQ's for fluticasone propinate (0.1 pg/mL) and salmeterol (0.05 pg/mL).

A Forensic Toxicology Analysis of Synthetic Fentanyl Compounds in Whole Blood Using Oasis Prime MCX and Waters TQ-S Micro

This poster was presented at the 2018 ASMS annual conference from June 3-7 in San Diego, CA.

A Clinical Research Method for the Analysis of Serum Testosterone and Androstenedione

An analytically sensitive and selective clinical research method has been developed for the analysis of serum testosterone and androstenedione.

Analysis of Serum Adrenal Steroids Using the ACQUITY UPLC I-Class with Xevo TQD for Clinical Research

This technology brief demonstrates the analytically sensitive and precise measurement of adrenal steroids from limited-volume clinical research serum samples.

Multiplexed Analysis of Steroid Hormones Using ionKey/MS

In this application, we report the use of the newly developed 150-μm ionKey/MS System for the multiplexed quantitation of five steroid compounds in human serum.

Analysis of Testosterone, Androstenedione, and Dehydroepiandrosterone Sulfate in Serum for Clinical Research

This application note describes a clinical research method utilizing Oasis PRiME HLB μElution Plate technology for the extraction of testosterone, androstenedione, and DHEAS from serum.