Self-Classified Topic Area(s): Small Molecules / Tox / TDM
Development of a Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QTof MS) Method for the Screening of Antihypertensive Drugs in Urine
Alexander J Lawson (1), Helen Wiggins (1), Indranil Dasgupta (2) (1) Department of Clinical Chemistry, Immunology and Toxicology, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS FT, (2) Glaxo Renal Unit, Birmingham Heartlands Hospital, University Hospitals Birmingham NHS FT
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Alexander Lawson (Presenter) University Hospitals Birmingham NHS FT
Presenter Bio: Alex Lawson is a Consultant Clinical Scientist and Forensic Toxicologist at Heartlands Hospital, Birmingham. He has a BSc, MSc and PhD in Biochemistry from the University of Birmingham and has been working as a clinical scientist since 2010.
In 2013, Alex co-founded the Toxicology Laboratory at Birmingham Heartlands Hospital. This department offers a comprehensive analytical and interpretive service for the investigation of acute poisoning and health monitoring. In this role Alex developed a large number assays for drug screening and quantitation using a number of chromatographic techniques with and without mass spectrometry. He also has extensive experience in the analysis of trace elements. Recent research has been focused on screening for drug adherence in chronic disease such as hypertension and on using high resolution mass spectrometry to identify novel psychoactive substances.
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
Background: Arterial hypertension is one of the most preventable causes of premature morbidity and mortality with resistant hypertension reported to be present in 5 to 30% of the total hypertensive population. Despite the poor prognosis, as many as 53% of those with resistant hypertension are reported to be non-adherent to their prescribed medication. This has led ourselves and others to develop LC-MS/MS methods to screen for the presence of antihypertensive drugs in urine. Despite the success of these assays, many suffer from not offering sufficient analytical breadth to cover all drugs prescribed in hypertension and/or not being able to identify key metabolites for some classes of drugs. Therefore we have developed a novel method for the detection of 49 commonly prescribed antihypertensive, antidiabetic and cardiovascular disease reducing medications in urine using LC-QTof MS.
Methods: Urine samples from 50 patients attending the hypertension clinic were analysed using an existing LC-MS/MS method and the LC-QTof MS method. For the LC-QTof MS method, urine samples were prepared using solid phase extraction and analysed using a Waters Xevo G2-XS LC-QTof MS system. Results obtained, and limit of detection for a number of drugs, were compared between the two methods.
Results: Limit of detection was comparable between the two methods with the majority of drugs detectable at 1 ng/mL. The newer LC-QTof MS detected all drugs found using LC-MS/MS in addition to drugs not screened for by the existing methodology. Felodipine, lercanidipine and lacidipine could not be identified in the urine of patients who were prescribed these drugs. However, using MSE we were able to identify metabolites of these drugs (termed felodipine M3, lercanidipine PA3 and lacidipine M3) in these patients.
Conclusions: The LC-QTof MS method presented here shows similar sensitivity to existing LC-MS/MS assays but is able to screen for more drugs and metabolites and, due to the nature of data acquisition, is flexible should more drugs need to be added to the screen. The results presented here also show that interrogation of MSE datasets is a suitable technique to identify metabolites of drugs of interest should parent compounds not be present in target biological matrices.
= Discovery stage.
= Translation stage.
= Clinically available.
