It’s well known that LC-MS (Liquid Chromatography Mass Spectrometry) is a highly powerful tool for analytical detection of compounds and employed in a wide variety of industries. From environmental labs to pharmaceutical manufacturers, the synergy of physical separation and compound (mass) identification has been a gold-standard method for many decades.
Taking this into account it is no surprise that LC-MS is increasingly used and of great importance for routine therapeutic drug monitoring (TDM). TDM being the clinical practice of measuring specific drugs at a designated timeframe, to optimise a dosing regimen in a patient and attain a constant concentration of the drug within the bloodstream [1].
Let’s dive into why methods employing LC-MS are being frequently developed and utilised within the sector, and what will come of LC-MS drug analysis in the future.
Why LC-MS?
It’s important to note that there are a wide variety of compounds that fall under the umbrella term of ‘therapeutic drugs’. From anti-infectives to immunosuppressives, LC-MS can be employed in TDM for a large variety of drug types. Compared to other methods currently employed in TDM, LC-MS offers increased sensitivity and specificity, both crucial for effective TDM.
Compounds without natural chromophores and fluorophores are notoriously difficult to quantify through classic methods of TDM. LC-MS has been shown to be the only (currently) viable method for detection and quantification of these compounds.
Looking to the future
One of the major downsides of LC-MS/MS is that it is a far more involved technique than competitors (such as ELISA). However as LC-MS technology has developed, this barrier has been dramatically reduced. Between improvements to online solid phase extraction and they development of pipetting robots (automation), LC-MS/MS is becoming far more accessible for TDM use.
Another pitfall commonly observed in LC-MS TDM assays is the lack of standardisation between laboratories. A wide variety of factors can range dramatically between labs, from sample storage to rejection methods, leading to a wide range of results and quality of data. A relatively recent review [2] explored different leading TDM methods and found that the time between sample extraction and analysis could range from a few hours to a whole week.
Standardisation, optimisation of sample type and consistent training moving forwards would greatly improve the reliability of LC-MS TDM methodology going forward and ensures a high level of analytical quality.
Conclusion
The clinical benefits of TDM are well proven, and LC-MS/MS is rapidly becoming an attractive and convenient method for therapeutic drug monitoring in clinical laboratories. Improvements need to be made to maximise the consistency and impact of LC-MS/MS analysis, but with commitment to optimisation and training, it will likely overtake competitive methods of TDM due to superior sensitivity and specificity.
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Sources
[1] Kang, J and Lee, M. (2009) Overview of Therapeutic Drug Monitoring. Korean J Intern Med. 2009 Mar; 24(1): 1–10.
[2] Seger, C. et al. (2016) Assuring the Proper Analytical Performance of Measurement Procedures for Immunosuppressive Drug Concentrations in Clinical Practice: Recommendations of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology Immunosuppressive Drug Scientific Committee, Therapeutic drug monitoring 38(2):170-189.