RESUMEN
Through blocking the cardiac persistent sodium current, riluzole has the potential to prevent myocardial damage post cardiac bypass surgery. A sensitive UHPLC-MS/MS method was developed and validated for quantitation of riluzole and 5-methoxypsoralen in human plasma and myocardial tissue homogenate using a liquid-liquid extraction with dichloromethane. The chromatographic separation was achieved using Shimadzu Shim-pack XR-ODS III, 2.0 × 50 mm, 1.6 µm column with a gradient mobile phase comprising methanol and ammonium acetate buffer pH 3.6 in purified water. The analyte and internal standard were separated within 3.5 min. Riluzole quantitation was achieved using the mass transitions of 235-138 for riluzole and 217-156 for 5-methoxypsoralen. The method was linear for riluzole plasma concentrations from 0.2 to 500 ng/mL and myocardial tissue homogenate concentrations from 0.2 to 100 ng/mL. The method developed was successfully applied to a clinical study for patients receiving riluzole while undergoing cardiac bypass surgery.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Miocardio/química , Fármacos Neuroprotectores/análisis , Riluzol/análisis , Espectrometría de Masas en Tándem/métodos , Procedimientos Quirúrgicos Cardíacos , Humanos , Modelos Lineales , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacocinética , Fármacos Neuroprotectores/uso terapéutico , Reproducibilidad de los Resultados , Riluzol/química , Riluzol/farmacocinética , Riluzol/uso terapéutico , Sensibilidad y EspecificidadRESUMEN
PURPOSE OF REVIEW: The characteristics of an ideal intravenous fluid in the critically ill patient are discussed. RECENT FINDINGS: Intravenous fluids are the most frequent drug administered to patients. Questioning the use of commonly administered intravenous fluids has resulted in an increased focus on their efficacy and safety. Discrimination between fluids currently in use has been the central theme of many recent large studies, and emerging from these findings is an understanding of characteristics that would make for an ideal fluid for critically ill patients. There is increased morbidity and mortality with high chloride-containing crystalloid solutions and hydroxyethyl starch preparations, with resultant international governmental agency warnings regarding hydroxyethyl starch . The ideal fluid is one which achieves the aim of administration while minimizing or negating adverse effects, is inexpensive, and sufficiently stable when stored to be used in a wide range of clinical settings. SUMMARY: The ideal fluid currently does not exist. Of existing options, use of hydroxyethyl starches and high chloride-containing crystalloid solutions should be discouraged. There is a lack of direct evidence that a balanced crystalloid solution confers benefit, however, the trend of recent data would support future investigation into the advantage of balanced solution over 0.9% saline.