ABSTRACT
Cardiovascular pharmacological countermeasures will be required as a preventive measure of cardiovascular deconditioning and early vascular ageing for long term space travelers. Physiological changes during spaceflight could have severe implications on drug pharmacokinetics and pharmacodynamics (PK/PD). However, limitations exist for the implementation of drug studies due to the requirements and constraints of this extreme environment. Therefore, we developed an easy sampling method on dried urine spot (DUS), for the simultaneous quantification of 5 antihypertensive drugs in human urine: irbesartan, valsartan, olmesartan, metoprolol and furosemide analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), considering spaceflight parameters. This assay was validated in terms of linearity, accuracy, and precision with satisfactory results. There were no relevant carry-over, matrix interferences. The targeted drugs were stable in urine collected by DUS until 6 months at +21 °C, +4°C, -20 °C (with or without desiccants) and at 30 °C during 48 h. Irbesartan, valsartan and olmesartan were not stable at 50 °C during 48 h. This method was found to be eligible for space pharmacology studies in terms of practicality, safety, robustness and energy costs. It has been successfully implemented in space tests programs led in 2022.
Subject(s)
Cardiovascular Agents , Tandem Mass Spectrometry , Humans , Tandem Mass Spectrometry/methods , Chromatography, Liquid/methods , Irbesartan , Valsartan , Dried Blood Spot Testing/methods , Reproducibility of ResultsABSTRACT
High blood pressure is the number one killer in the world. About 1.5 billion people suffered from hypertension in 2010, and these numbers are increasing year by year. The basics of the management of high blood pressure are described in the Canadian, American, International and European guidelines for hypertension. However, there are similarities and differences in the definition, measurement and management of blood pressure between these different guidelines. According to the Canadian guidelines, normal blood pressure is less than 140/90 mmHg (systolic blood pressure/diastolic blood pressure). The AHA and ESC estimate normal blood pressure to be less than 120/80 mmHg (systolic blood pressure/diastolic blood pressure). Regarding treatments, the AHA, ISH and ESC are also in agreement about dual therapy as the first-line therapy, while Canadian recommendations retain the idea of monotherapy as the initiation of treatment. When it comes to measuring blood pressure, the four entities agree on the stratification of intervention in absolute cardiovascular risk.
