MSACL 2023 Abstract

Laboratory Automation to the Rescue: Evolution of the Clam Platform for Automated LC-MS/MS Sample Preparation

Eishi Imoto (1), Daisuke Kawakami (2), Milaan Thirukumaran (3), Jonathan Ferguson (3), Rachel Lieberman (3), Masayuki Nishimura (3), Alvin Hoang (3) and Scott Kuzdzal (3).
(1) Shimadzu Corporation, Kyoto, Japan, (2) Shimadzu Europa GmbH, and (3) New Strategy Department, Shimadzu Scientific Instruments, Columbia, Maryland, USA

Scott Kuzdzal, Ph.D., Analytical Chemistry (Presenter) Shimadzu Scientific Instruments

Presenter Bio: Dr. Scott Kuzdzal received a Ph.D. from the University of California at Riverside. He served as a postdoctoral fellow at the Johns Hopkins University School of Medicine, where he co-founded and directed the Johns Hopkins Center for Biomarker Discovery with Dr. Daniel Chan. Dr. Kuzdzal assisted in the completion of the Human Genome Project, working with Celera Genomics.

In addition to extensive industrial research experience, Dr. Kuzdzal has a strong medicinal and clinical chemistry background and has directed Toxicology and Therapeutic Drug Monitoring Labs at Johns Hopkins Medical Institutions. He currently serves on the editorial review board of Proteomics. He has published protein and peptide biomarkers for pancreatic cancer (HIPAP1), Alzheimer’s disease and ovarian cancer using a wide variety of separation and detection methods. Scott has lectured at continuing medical education courses at Johns Hopkins Hospital, George Mason University/INOVA Fairfax Hospital and the NIH, as well as conferences worldwide. Scott currently serves as the Vice President of the New Strategy Department at Shimadzu Scientific Instruments. He has created many products and brands, such as Kick Some Mass™, Analytical Intelligence™, MegaTOF™ and the Cannabis Analyzer.

Dr. Kuzdzal has over 350 scientific manuscripts, book chapters and presentations. His passion is improving clinical and QC laboratory testing, and development of new, integrated health systems.

Publications: https://independent.academia.edu/ScottKuzdzal

Relevant Financial Disclosures (within past 24 months) Honorarium/Expenses Shimadzu Grant/Research Support Shimadzu Committee/Board/Advisory Board Shimadzu Scientific Instruments Executive Committee Salary Shimadzu Conflict mitigation NOT REQUIRED.

Introduction
Laboratory medicine is a critical component of the complex U.S. healthcare system. Since the onset of the COVID-19 pandemic, laboratory personnel have taken on greater responsibility, working longer days, picking up extra shifts and in some cases even working across multiple labs to keep up. Laboratory automation removes a lot of repetitive work required of lab professionals, increasing laboratory efficiency by providing consistent productivity and quality. LCMSMS sample prep can be automated with excellent accuracy and reproducibility on the new Shimadzu LCMS-2040 platform. Automation reduces method variability, the chance of sample mix-ups and the risk of exposure to samples.

Methods
The analysis was performed on human plasma samples using a Shimadzu LCMS-8060 triple quadrupole mass spectrometer equipped with a clinical laboratory automation module (CLAM) for fully automated sample preparation and a Nexera X2 UHPLC with a Shim-pack Scepter C18-120 column (2.1 mm I.D. × 50 mm, 1.9 μm) in ESI positive mode.

Preliminary Data
We herein demonstrate automation of the analysis of the antiviral remdesivir and its main plasma metabolite, GS-441524, a nucleoside analogue antiviral drug, with excellent accuracy and reproducibility. We also describe recent innovations in the CLAM automated sample preparation platform. Mass spectrometric chromatograms of Remdesivir and GS-441524 are demonstrated in plasma with good accuracy and reproducibility. The repeatability of less than 4% RSD and the accuracy between 89-106% on each control sample confirmed the robustness and the efficiency of this method (n=6). Several hardware modifications are herein presented, which result in enhanced ease of use as well as performance improvements. A forensic toxicology database for LC-MS/MS was added and the CLAM is now able to connect to a Laboratory Information System (LIS) for bidirectional communications.

Novel Aspect
Advances in full automation of LCMS sample preparation for the analysis of antiviral drugs is presented. These innovations improve CLAM automated sample preparation for the clinical research of anticoagulants, immunosuppressants, toxicology (STAT screens), methylmalonic acid (MMA), anti-epileptics, amino-glycoside antibiotics, antiarrhythmic drugs and beta-blockers.