ABSTRACT
Adherence to cardiovascular preventive agents is important to prevent short and long term cardiovascular events. Recently, qualitatively compound screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has gained interest for drug adherence assessment in patients at high risk of cardiovascular events. Therefore, we developed and tested an assay including 52 compounds and metabolites, covering over 95% of the antihypertensive and antithrombotic agents available worldwide. Trichloroacetic acid was used as simple and fast method for protein precipitation. The assay was validated for lower limit of quantification (LLOQ), linearity, stability for freeze/thaw, room temperature, autosampler and matrix effects. The LLOQ for each compound was targeted under the population trough concentration (PTC) as reported in literature to assure high sensitivity for adherence detection. This was accomplished for 50 of 52 compounds with a LLOQ equal or lower compared to the PTC. Linearity was confirmed for all compounds (r2â¯>â¯0.995), except for acetylsalicylic acid (r2â¯=â¯0.991). For room temperature stability, 12 compounds showed degradation over 20% after 20â¯h. 3 compounds suffer from matrix effect with recoveriesâ¯<â¯50%. After analytical validation, blood samples from 91 patients with difficult-to-treat hypertension were analyzed. Patients were unaware of adherence assessment. Adherence varied largely per agent and per concentration ratio (CR) (ratio of the detected concentration with LC-MS/MS and the PTC) cut-off value. Additionally, stratification by adherence group showed that the percentage of patients classified as non-adherent increased from 6.6% for qualitative analysis (pos/neg) to 19.8% for a CR cut-off of 0.5. The data imply that using the CR cut off values has a significant and relevant effect on patient adherence classification.
Subject(s)
Antihypertensive Agents/blood , Antihypertensive Agents/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Drug Monitoring/methods , Tandem Mass Spectrometry/methods , Antihypertensive Agents/chemistry , Humans , Hypertension/drug therapy , Limit of Detection , Linear Models , Medication Adherence , Reproducibility of ResultsABSTRACT
A survey of carcinoma of the oesophagus at Kalafong Hospital revealed a greater incidence of the disease in males, being highest in the age group 50 - 59 years, with the middle third of the oesophagus the most prevalent site and with oesophagotracheal or oesophagobronchial fistulae a common complication.
