NACCCA proudly sponsored the 8th Clinical Application Training Course on Liquid Chromatography-Mass Spectrometry Technology, held in collaboration with the Fudan Zhongshan hospital Clinical Laboratory Science Department. The event took place from October 23 to 25, 2023, and was organized in partnership with Mass Spectrometry-Applications to the Clinical Lab (MSACL) from the United States, the Chinese Medical Association's Committee on Clinical Laboratory Medicine Education, and the Shanghai Biomedical Engineering Society's Committee on Clinical Laboratory Medicine & the Mass Spectrometry Group of the Clinical Laboratory Medicine Branch of the Shanghai Medical Association.

Seven NACCCA speakers delivered presentations covering various topics, including the forefront of liquid chromatography-mass spectrometry technology, fundamental theories, method development and validation, daily operation and quality management, clinical applications, and proteomics applications.

Dr. Zhang Yan, the founding chair of the Mass Spectrometry Division of the American Association for Clinical Chemistry (AACC) and the president of NACCCA in 2015, delivered a keynote presentation titled "Future Development Trends in Mass Spectrometry Testing - Automation and Protein Analysis." Dr. Zhang Yan highlighted two crucial aspects of the future development of mass spectrometry testing. Firstly, in terms of automation, Dr. Zhang presented two automation models: Standalone LC-MS/MS and LC-MS/MS line. Despite its discontinuation in 2023, the automated instrument Cascadion demonstrated commendable performance during the testing phase. Secondly, Professor Zhang discussed the development of proteomics in clinical applications, addressing the necessary shift in mindset from research and development to clinical application, variations in regulatory systems, and the extension to FDA approval pathways and LDT (Laboratory Developed Test) pathways.

Dr. Yuan Chao, who served as the President of NACCCA in 2019 and hails from the Clinical Mass Spectrometry Laboratory at Quest Diagnostics in the United States, delivered three presentations at the teaching course. He provided a systematic overview of the fundamental principles and instrument construction of liquid chromatography. In his second presentation, Dr. Yuan Chao summarized that sample preprocessing addresses two major challenges: the complexity of sample components, which cannot be directly injected, and the high precision requirements of mass spectrometers, necessitating a high degree of cleanliness in samples, thus requiring preprocessing. Drawing on his own work experience, Dr. Yuan provided a clear and in-depth overview of application scenarios, advantages, disadvantages, and considerations of various preprocessing methods. Furthermore, Dr. Yuan Chao emphasized the importance of maintenance and troubleshooting in liquid chromatography applications, suggesting that mass spectrometry laboratories should keep records of equipment failures. He provided a detailed overview of troubleshooting strategies, explaining how to simplify complex issues and effectively address common problems encountered in most laboratories. Dr. Yuan pointed out that 90% of instrument malfunctions are caused by chromatography issues, elaborating on potential reasons for elevated column pressure, sample injection failures, retention time drift, the absence of chromatographic peaks, and signal loss in mass spectrometry, providing valuable insights and methods for problem-solving in daily work.

Dr. Weijia Wu, Chief Scientific Officer of Caliber Precision Medicine, who served as the President of NACCCA in 2014, discussed the application areas of clinical mass spectrometry in North America, the automation and throughput of clinical mass spectrometry, the hormone standardization project at the Centers for Disease Control and Prevention (CDC), and the coverage audit by U.S. health insurance. Dr. Wu emphasized that the development of clinical mass spectrometry requires collaboration among teams, involving government regulation, manufacturers, and monitoring agencies working together.

Dr. Yusheng Zhu, medical director from the Laboratory of Penn State University Hershey Medical Center, United States, and the President of NACCCA in 2012, introduced the guiding document CLSI C62-A regarding method establishment and performance validation. He pointed out that the development of LC-MS/MS methods is a step-by-step optimization process. Whether it's the initial tuning of the mass spectrometry, optimization of chromatographic conditions, or the selection of sample extraction methods, each step should be tackled from easy to difficult. Dr. Zhu detailed the methods of performance validation and acceptable standards, including precision, accuracy, sensitivity, linearity, interference, reference intervals, carryover contamination, matrix effects, recovery, and stability, aiming to ensure the reliability and accuracy of test results through thorough performance validation.

Dr. Xin Yi, from the Houston Methodist Hospital Laboratory and NACCCA 2022 President, gave presentations on "Quality Control and Quality Assurance in Mass Spectrometry Detection" and "Current Status and Advances in Clinical Proteomics." Dr. Yi emphasized the importance and specificity of quality control in clinical mass spectrometry methods. She elucidated the selection of quality control metrics and validation standards, as well as the parameter recording and result review in the experimental process. Establishing clear standardized operating procedures, straightforward record-keeping methods, and effective monitoring processes can directly and effectively control every aspect of clinical mass spectrometry methods, ensuring the accuracy and reliability of laboratory results. Dr. Yi stressed the need to strike a balance between experimental efficiency and reliable results.  In the past decade, mass spectrometry technology has made significant advancements in clinical proteomics, with many successful recent cases. Dr. Xin Yi provided a detailed overview of protein quantification and qualitative analysis, including targeted protein quantification, the detection of IGF-1, thyroglobulin, monoclonal antibody drugs, lipoproteins, amyloid typing, monoclonal immunoglobulin diseases, and membranous nephropathy using proteomics. Dr. Yi also noted that while research in this area has been growing steadily, the methods that can be translated into clinical diagnostics remain limited. These methods are primarily conducted as in-house projects in a few specialized laboratories, and their results are often considered research-oriented. They have not yet gained widespread acceptance in clinical practice, and there is a need for cross-center clinical validation studies to demonstrate their clinical utility.

Dr. Cao Jing, from the University of Texas Southwestern Medical Center, and NACCCA President 2020, provided an overview of the history and current state of newborn genetic disease screening, as well as the criteria for selecting diseases to be screened in newborns. She then discussed the biomarkers used in the screening and diagnosis of genetic diseases, such as plasma amino acids, urinary organic acids, and adrenal hormones. Finally, she Cao introduced the use of high-resolution mass spectrometry for diagnosing hemoglobinopathies.

Dr. He Yang, from the New York-Presbyterian Hospital, and President of NACCCA 2023, shared insights into the working principles of ICP-MS, the selection of different modes, the advantages of ICP-MS over atomic absorption spectroscopy and atomic emission spectroscopy, considerations in method development and quality control, and clinical applications. She discussed the clinical cases and detection methods for toxic heavy metals such as lead, mercury, arsenic, cadmium, and thallium and discussed the unique interferents and solutions for different elements and how to choose the appropriate biological sample type for each element. She also addressed considerations in pediatric blood lead testing and provided an analysis of clinical cases.

NACCCA members have made a significant contribution to the 8th Mass Spectrometry Application Training Course. This conference provided experts and students with a platform for learning and communication, promoting the popularization and scientific development of liquid chromatography-mass spectrometry technology. Students have shown great enthusiasm, and they look forward to seeing each other again next year!