Sample Matrices for Mass Spectrometry-Based Adherence Monitoring: A Systematic Critical Review

Background:Analytical monitoring of adherence using mass spectrometry (MS) plays an important role in clinical toxicology. Unambiguous detection of drugs (of abuse) and/or their metabolites in body fluids is needed to monitor intake of medication as prescribed or to monitor abstinence as a follow-up to detoxification procedures. This study focused on the advantages and disadvantages of different sample matrices used for MS-based adherence monitoring.Methods:Relevant articles were identified through a literature search in the PubMed database. English articles published between January 01, 2017, and December 31, 2022, were selected using the keywords "adherence assess*" or "adherence monit*" or "compliance assess*" or "compliance monit*" in combination with "mass spectrom*" in the title or abstract.Results:A total of 51 articles were identified, 37 of which were within the scope of this study. MS-based monitoring was shown to improve patient adherence to prescribed drugs. However, MS analysis may not be able to assess whether treatment was rigorously followed beyond the last few days before the sampling event, except when hair is the sample matrix. For medication adherence monitoring, blood-based analyses may be preferred because reference plasma concentrations are usually available, whereas for abstinence control, urine and hair samples have the advantage of extended detection windows compared with blood. Alternative sample matrices, such as dried blood samples, oral fluid, and exhaled breath, are suitable for at-home sampling; however, little information is available regarding the pharmacokinetics and reference ranges of drug (of abuse) concentrations.Conclusions:Each sample matrix has strengths and weaknesses, and no single sample matrix can be considered the gold standard for monitoring adherence. It is important to have sufficient information regarding the pharmacokinetics of target substances to select a sample matrix in accordance with the desired purpose.