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
Synthetic cannabinoids are becoming increasingly popular as substances of abuse. However, in the Netherlands synthetic cannabinoid intoxications are rare. We report a 16-year-old male who became deeply comatose and was admitted to the intensive care unit for invasive mechanical ventilation after a buse of aninitially unknown drug. Routine toxicology screening with an immunoassay only detected tetrahydrocannabinol, but additional tests with liquid chromatography mass spectrometry revealed synthetic cannabinoid use. This case underlines the challenging diagnosis of synthetic cannabinoid intoxications and the severe complications they can produce.
Subject(s)
Cannabinoids/toxicity , Coma/chemically induced , Nervous System Diseases/chemically induced , Adolescent , Humans , Male , NetherlandsABSTRACT
The release of vitamin B12 (1355 Da) from matrices based on multiblock copolymers was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion method. The copolymer properties, like permeability, could be varied by increasing the PEG-segment length from 300 up to 4,000 g/mol and by changing the wt% of PEGT. From permeation and release experiments. the diffusion coefficient of vitamin B12 through PEGT/PBT films of different compositions was determined. The diffusion coefficient of Vitamin B12 was strongly dependent on the composition of the copolymers. Although an increased wt% of PEGT (at a constant PEG-segment length) resulted in a higher diffusion coefficient, a major effect was observed at increasing PEG-segment length. By varying the copolymer composition, a complete release of vitamin B12 in 1 day up to a constant release for over 12 weeks was obtained. The release rate could be effectively tailored by blending copolymers with different PEG-segment lengths. The swelling and the crystallinity of the matrix could explain the effect of the matrix composition on the release behavior.
