Pittcon 2024: High Throughput Drug Analysis by LC–MS and its Challenges

Perry Wang from the U.S. FDA chaired this session on high-throughput analysis in the pharmaceutical sector using liquid chromatography mass spectrometry (LC–MS) at Pittcon in San Diego.

The session began with a presentation by Bingchuan Wei, senior principal scientist at Genentech, on “Speeding Up Pharmaceutical Analysis with Emerging Analytical Technologies.” This talk highlighted the important role that recent advances in high performance liquid chromatography and spectroscopy play in the chemistry, manufacturing and control (CMC) of important pharmaceuticals. These advances contribute to specific product quality attributes (PQAS) and provide the analyst with information to guide effective control strategies in pharmaceutical development.

Aihua Liu, senior director of Bioanalysis at Resolian then presented on “Pros and Cons of Different Chromatographic Technologies in High-Throughput Bioanalysis of Oligonucleotide Therapeutics.” Liu emphasized that precise and efficient bioanalytical methods pay a pivotal role in the development of successful oligonucleotide (ON)-based drugs, but this type of analysis can often be challenging. Liu’s team have extensive practical experience in the development and validation of many bioanalytical methods for different types of ONs, including tandem mass spectrometry hyphenated to reversed-phase liquid chromatography, ion pair liquid chromatography, or hydrophilic interaction liquid chromatography. The team also used ion-pair liquid chromatography high resolution mass spectrometry, and ion exchange liquid chromatography with fluorescence detection. The advantages and disadvantages of each technique for the high-throughput bioanalysis of various ONs, including antisense oligonucleotides and small interfering RNAs of varying lengths, were described with examples from case studies

Tao Chen from Genentech then presented on “High Throughput LC–MS Analysis for High-Throughput Experimentation.” Chen highlighted the importance of high-throughput experimentation (HTE)–defined as the workflow of running multiple reactions, such as 96 in parallel— in pharmaceutical drug discovery and development. The importance ofdifferent LC–MS techniquesto achieve high throughput analysis ofsamples were described as well as practical insights into data processing.

The session concluded with a presentation by Xin Di from Shenyang Pharmaceutical University with a talk entitled “Simultaneous Determination of Oligosaccharides and IIridoid Glycosides in Rat Plasma using HILIC–MS/MS and its Application to Pharmacokinetic Study of Rehmannia glutinosa Extract.” The challenges and development of a fast and sensitive method for the quantitative analysis of oligosaccharides and iridoid glycosides using hydrophilic interaction chromatography coupled with tandem mass spectrometry were described. The method developed was used to determine raffinose, manninotriose, stachyose, ajugol, and catalpol in rat plasma. Challenges in method developing this method included different retention behaviors, split peaks, low ionization efficiency, thermal instability, and reduced column performance. Strategies to address these challenges involved optimizing chromatography, mass spectrometry, and sample preparation techniques. The method achieved effective separation using specific conditions and could detect concentrations as low as 0.01–0.2 µg/mL with 50 µL of plasma sample. The new technique was successfully applied to study the pharmacokinetics of oligosaccharides and iridoid glycosides in normal and type 2 diabetic rats after administering Radix Rehmanniae extract orally.