The Benefits of LC-MS Drug Testing: High Sensitivity and Specificity in Action
Over the past decade, mass spectrometry liquid chromatography (LC-MS) testing has been rapidly employed across multiple diagnostic domains. Today, LC-MS and LC-MS/MS analysis form a crucial part of clinical toxicology, therapeutic drug monitoring, inborn errors of metabolism, and endocrinology research. Due to higher selectivity and sensitivity than other methods, such as immunoassays, LC-MS drug testing is often irreplaceable in certain circumstances.
However, LC-MS labs offering LC-MS method development and conduct may face difficulties in initial setup days. However, higher acquisition costs and increased preliminary testing expenditure can be easily overcome by performing multiplex analysis. In this comprehensive article, we shall dive deeper into LC-MS systems employed in different applications such as ADA analysis and therapeutic drug monitoring.
Clinical Toxicology
LC-MS systems offer enhanced flexibility, specificity, and sample throughput compared to methods such as immunoassays and gas chromatography-mass spectrometry. Hence, they have seen tremendous growth in routine laboratory testing.
For example, GC-MS systems have been a gold standard over immunoassays for identifying unknown abused drugs. However, for desired resolution and sensitivity, most compounds required derivatization to make them volatile and compatible with gas chromatography. On the other hand, LC-MS systems can handle non-volatile molecules and do not require extensive sample preparation.
Endocrinology
Due to its ease of use and rapid analysis, immunoassays are often used in endocrinological investigations. However, in some cases, these automated systems are not suitable or available. Besides, these assay formats have issues with cross-reactivity and interference. The specificity of MS units has revealed the limitations of multiple immunoassays in measuring steroid hormones accurately. In these cases, many laboratories and research studies are now opting for LC-MS and LC-MS/MS-based approaches for accurate and reliable patient diagnosis.
Metabolic disorders
Metabolites are chemically diverse and have a dynamic concentration range. Hence, they have always posed challenges while analyzing human samples. However, advanced systems such as LC-MS testing have proven vital in metabolomic research, facilitating the exploration of metabolomics in a deep and satisfactory manner.
Moreover, advances in LC-MS development have improved the diagnostic specificity and sensitivity when assessing disease markers such as amino acids, lipids, amines, vitamins, organic acids, and lipids. For example, while screening for inborn metabolism errors, LC-MS approaches have facilitated the simultaneous detection of analytes, improving patient outcomes through early identification and treatment.
Therapeutic drug monitoring
Monitoring drug therapeutics such as immunosuppressants has benefited from increased selectivity and sensitivity of LC-MS methods. In certain situations, LC-MS assays may be the only method to quantify drugs without natural fluorophores or chromophores. LC-MS assays, however, require a more involved approach compared to alternatives such as automated immunoassays. Hence, it requires compliance with regulatory guidelines when developing the technology.
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Toxicology
LC-MS systems are ideal for toxicological studies as they can offer greater confidence in determining and identifying a broad range of toxins, drugs, and metabolites. However, LC-MS systems face some issues in toxicological analysis. Product ion spectra of LC-MS assays can vary between instruments. Besides, LC-MS methods do not have comprehensive spectral libraries. Secondly, unlike GC-MS, LC-MS systems do not have a set of operating conditions for most analytes. Different target analytes have unique optimal parameters requiring assessment on a case-to-case basis. Hence, most toxicological evaluations depend on targeted panels that can contain multiple drugs and their metabolites.
Today, multiple strategies for clinical toxicological screening using LC-MS assays are published and developed. Researchers can perform direct urine analysis with LC-MS systems. Some potential pitfalls may occur. However, they can be eliminated by matching the mass spectra and retention times to a standard. Besides, the sensitivity of LC-MS assays allows the assessment of hair samples and oral fluids.
There is considerable demand for LC-MS testing in vitamin D estimations due to differences observed in commercial immunoassay readings. Several LC-MS assays for vitamin D in plasma and serum have been developed. Besides, derivatization is employed to enhance the sensitivity for detecting metabolites present at low levels.
The road ahead for LC-MS testing
Modern mass spectrometers are selective and sensitive. Hence, LC-MS testing is gradually replacing several immunoassays. Although the initial setup costs are relatively high for LC-MS assays, they have long-term cost savings compared to commercial immunoassays. Not to mention, strategies are emerging for quantitative and sensitive multiplex LC-MS analysis of proteins and peptides. As the sensitivity of mass spectrometers continues to improve, existing immunoassays will be soon replaced by advanced LC-MS assays.
Another significant advantage of LC-MS assays is the ability to analyze multiple analytes in a single run. This feature has the potential to generate additional useful information and simplify laboratory setup. LC-MS setups that can detect hundreds of target analytes in a single assay run are being developed, where the multiplexing capacities are exponentially increasing. LC-MS testing will be probably employed widely in clinical biochemistry when multiplexed approaches can generate data to justify the initial higher acquisition costs.
