RESUMEN
A patient admitted to hospital died shortly after admission without a proper diagnosis having been made. Symptoms as well as the presence of a brown powder found in the possession of the deceased indicated the possibility of cantharidin intoxication. Cantharidin was positively identified by means of a GC/MS analysis, utilizing the selected ion monitoring technique (SIM), for m/z = 197.0813, (M + H+) for cantharidin, under positive chemical ionization conditions at a resolution of 7000 and a mass window of 30 ppm. Quantitation was done by means of a GC/MS SIM analysis of a toluene extract of acidified post-mortem serum under El+ conditions at a resolution of 3000, using clofibrate as internal standard and monitoring m/z = 128.0473 and 128.0029 for cantharidin and clofibrate respectively. The post-mortem serum was found to contain cantharidin at a concentration of 72.3 ng/ml whilst the cantharides powder contained 0.87% cantharidin.
Asunto(s)
Cantaridina/análisis , Adulto , Cantaridina/envenenamiento , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Cambios Post MortemRESUMEN
The bio-availability of four warfarin tablet formulations--Marevan (Allen & Hanburys); Warfarin (Petersen); Coumadin (Boots) and Warfarin (Lennon)--administered as a single 10 mg oral dose, was compared in a single-blind cross-over study. Twelve healthy adult male volunteers participated in a clinical trial in which 95% confidence intervals for the true ratio (of the means) of each test product with respect to the reference product (Marevan) were calculated for maximum concentration and area under the plasma concentration time curve. The three test products differed by less than 20% from the reference product, suggesting that all four can be used interchangeably without risk of compromising safety and efficacy.
Asunto(s)
Warfarina/farmacocinética , Adulto , Disponibilidad Biológica , Ensayos Clínicos como Asunto , Humanos , Masculino , Factores de Tiempo , Warfarina/sangreRESUMEN
A gas chromatographic-mass spectrometric (GC-MS) method utilising single-ion monitoring at a resolution of 3000 to quantitate cantharidin in post-mortem serum is described. Serum was acidified, extracted with toluene, and 1 microliter of the toluene extract subjected to GC-MS analysis. Clofibrate was used as internal standard. The method displayed a high degree of specificity and was accurate and precise, with a linear response in the concentration range 15-150 ng/ml. A cantharidin concentration of 72.3 ng/ml was found in the post-mortem serum.
Asunto(s)
Cantaridina/sangre , Cromatografía de Gases y Espectrometría de Masas , Humanos , Indicadores y Reactivos , SolucionesRESUMEN
Two commercially available blood collection systems (Venoject and Vacutainer) were investigated for their effect on the plasma concentrations of a variety of drugs. Vacutainer tubes adversely affected the following drugs: propranolol, penbutolol and quinidine, whereas Venoject tubes had no effect on the plasma concentrations of these drugs. Neither collection system had any effect on the plasma concentrations of the following drugs: acebutolol, the main metabolite of acebutolol (DL-1-(2-acetyl-4-acetamidophenoxy)-2-hydroxy-3-isopropylaminopropane), diazepam, N-demethyldiazepam, digoxin, ethosuximide, salicylic acid, valproic acid, warfarin and carbamazepine.
Asunto(s)
Recolección de Muestras de Sangre/instrumentación , Preparaciones Farmacéuticas/sangre , Acebutolol/sangre , Carbamazepina/sangre , Diazepam/sangre , Digoxina/sangre , Etosuximida/sangre , Humanos , Nordazepam/sangre , Penbutolol/sangre , Propranolol/sangre , Quinidina/sangre , Salicilatos/sangre , Factores de Tiempo , Ácido Valproico/sangre , Warfarina/sangreRESUMEN
Two spectrofluorimetric methods for the determination of dipyridamole in plasma are described. The thin-layer chromatographic-fluoridensitometric method utilizes 1 ml of plasma which is extracted at pH 10 with diethyl ether-dichloromethane (80:20). The organic phase is evaporated to dryness, reconstituted in 250 microliter dichloromethane and 5 microliter are spotted on a silica gel 60 plate. The plate is developed in ethyl acetate-methanol-ammonia (85:10:5), dried, dipped in a paraffin wax solution, dried, and scanned using 380 nm as excitation wavelength, a 430 nm cut-off filter, and collecting all emitted light on the photomultiplier. Quantitation was done by the external standard method, peak heights being measured and a calibration graph constructed. For the spectrofluorimetric method 1 ml of plasma is extracted at pH 10 with 8 ml of hexane-isoamyl alcohol (95:5) and the organic phase used directly for the measurement of the fluorescence intensity (excitation 405 nm, emission 495 nm). Quantitation was done by measuring the fluorescence of standards that were treated as above and constructing a calibration graph of concentration versus fluorescence intensity. Concentrations of unknowns were found by interpolation from this graph. The two methods were found to exhibit good correlation but the spectrofluorimetric method proved to be more amenable to the analysis of a large number of samples.
Asunto(s)
Dipiridamol/sangre , Espectrometría de Fluorescencia/métodos , Cromatografía en Capa Delgada/métodos , Dipiridamol/uso terapéutico , HumanosRESUMEN
When phenobarbitone was added to the treatment regimen of epileptic patients who received phenytoin only, the serum levels of phenytoin increased significantly within 6 weeks. Eleven weeks after the introduction of phenobarbitone, phenytoin levels had returned to those existing before phenobarbitone therapy. In view of possible complex pharmacokinetic interactions which might occur when phenobarbitone is added to a regimen of phenytoin, or vice versa, frequent measurement of serum drug levels appears to be indicated for up to 10 weeks after effecting a change in treatment. During this period a constant change in serum levels could be expected, resulting either in toxicity or lack of efficacy.
Asunto(s)
Epilepsia/sangre , Fenobarbital/sangre , Fenitoína/sangre , Adulto , Interacciones Farmacológicas , Quimioterapia Combinada , Epilepsia/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Fenobarbital/uso terapéutico , Fenitoína/uso terapéutico , Factores de TiempoRESUMEN
A sensitive and specific thin-layer chromatographic method for the simultaneous determination of acebutolol [DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane] and its major metabolite [DL-1-(2-acetyl-4-acetamidophenoxy)-2-hydroxy-3-isopropylaminopropane] is described. A 2-ml volume of serum with 350 ng of quinidine as internal standard was extracted at pH 10, the solvent was evaporated off and the residue was dissolved in 50 mul of methanol. A 10-mul volume of the solution was spotted on a thin-layer plate and after elution (ethyl acetate-methanol-ammonia, 75:20:5) the plate was dried at 90 for 15 min and, after cooling, dipped in a 10% paraffin wax solution. The fluorescence was measured using a spectrofluorimeter with a thin-layer scanning attachment. The peak-height ratios of acebutolol to internal standard and metabolite to internal standard were used to quantitate acebutolol and the metabolite, respectively.