A Novel ‘Dilute-and-Shoot’ Liquid Chromatography–Tandem Mass Spectrometry Method for the Screening of Antihypertensive Drugs in Urine

Arterial hypertension is one of the most preventable causes of premature morbidity and mortality with resistant hypertension reported to be present in 5-30% of the total hypertensive population. Despite the poor prognosis, as many as 53% of those with resistant hypertension are reported to be nonadherent to their prescribed medication. An objective test of adherence, which is easy to administer, quick, inexpensive and reliable, is therefore needed to identify patients with true resistance to antihypertensive drugs to optimize their treatment. We have developed a novel LC-MS-MS method for the detection of 23 commonly prescribed antihypertensive medications in urine. The validated method was subsequently applied to the analysis of urine from a cohort of 49 individuals who were taking at least one antihypertensive agent in the screening profile to determine their adherence. The screening method was found to be reproducible, sensitive and specific with the limit of detection ranging from 0.1 to 1.0 µg/L. Sample preparation is rapid (30 s) and simple, with a total analysis time of 11 min. The assay successfully identified the majority of drugs our cohort had admitted to taking (88%) with drugs not detected in urine, potentially indicating nonadherence to prescribed medication. The performance of this simple, robust LC-MS-MS procedure is suitable for screening urine for the presence of commonly prescribed antihypertensive medications. The assay, which can easily be implemented in other laboratories, has the potential to significantly improve investigation and management of resistant hypertension.