Simultaneous determination of clozapine, olanzapine and mirtazapine in human plasma by LC-MS/MS / 法医学杂志

OBJECTIVE@#To develop a method for determination of clozapine, olanzapine and mirtazapine in human plasma by liquid chromatography-tandem mass spectrometry(LC-MS/MS).@*METHODS@#Clozapine, olanzapine and mirtazapine were extracted from plasma samples by using diethyl ether and separated by Agilent Zorbax SB-C18 column(2.1 mm x 150 mm, 5 microm). Electrospray ionization source was applied, positive ion mode was used to detect and multiple reaction monitoring mode was used to quantify clozapine, olanzapine and mirtazapine. Carbamazepine was the internal standard.@*RESULTS@#The detection limits of clozapine, olanzapine and mirtazapine were within 0.41-0.92 ng/mL. The calibration curve in the concentration range of 10.0-2000.0 ng/mL showed a good linear distribution (r > or = 0.992 4). The average extraction recoveries were within 65.7%-94.2%. Intra-day RSD and inter-day RSD were less than 6% (n = 5).@*CONCLUSION@#This method seems to be quite specific, sensitive and accurate, and can be used to detect clozapine, olanzapine and mirtazapine in forensic and clinical analytic toxicology.

Clinical pharmacokinetics of benzodiazepines

The present article summarizes the clinical pharmacokinetic properties of benzodiazepines. The goal is to better prescribe these compounds in the field of anxiety, sleep disorders and as anticonvulsive drugs. All pharmacokinetic parameters are overviewed: absorption, blood protein binding distribution, metabolisation and half-lives. A new approach is tried to find relationship between brain concentrations and receptor bindings in the purpose of giving an explanation of their duration of effect

Comparison between propofol and midazolam/flumazenil as intravenous anaesthetic agents for minor outpatient surgery

Forty adult patients scheduled for minor urological surgical procedures were randomly allocated to two equal groups for anaesthesia. One group was administered propofol, a new class of intravenous anaesthetic agents chemically unrelated to the barbiturates, steroid or eugenol agents, the other group was given midazolam, a new short-acting benzo-diazepine. In both groups this was followed by fentanyl and nitrous oxide, but in the midazolam group flumazenil, a specific benzodiazepine antagonist, was administered at the end of surgery. Both techniques provided good-quality anaesthesia, and there was no difference in recovery times as judged by the patients' ability to open their eyes and give their date of birth. However, those who received propofol were able to sit up unaided significantly earlier and also to carry out the Postbox and Letter Deletion Tests significantly faster. After flumazenil reversal there was no significant difference in the sedation score for 30 min, but this was followed by a significant degree of resedation. The incidence of nausea, vomiting and headache were the same in both groups. This study showed propofol to be superior to midizolam followed by flumazenil reversal as the intravenous component of outpatient anaesthesia for minor urological surgical procedures

Un nuevo método radiorreceptor para la cuantificación de benzodiazepinas en fluidos biológicos / A new radioreceptor method for the quantification of benzodiazepines in biological fluids

Se desarrolló un método radiorreceptor, relativamente rápido y de bajo costo, para determinar concentraciones de benzodiazepinas en fluidos biológicos. El método se basa en el hecho que la cantidad de [3H]-flunitrazepam incorporada específicamente, por fotomarcado, en receptores de membranas sinaptosomales, está relacionada cuantitativamente con la cantidad de benzodiazepina no radiactiva presente en el medio de incubación. Después del fotomarcado, las membranas fueron tratadas con ácido tricloroacético, y el sedimento obtenido fue lavado con acetona para eliminar el [3H]-flunitrazepam remanente, no unido. La preparación de receptor, constituida por membranas liofilizadas obtenidas a partir de corteza de cerebro bovino, fue estable durante seis meses por lo menos. El análisis estadístico de los gráficos logit-log de las curvas de desplazamiento con varias benzodiazepinas, mostró los siguientes valores de IC50: clonazepam, 1,6 nM; flunitrazepam, 3,8 nM; nitrazepam, 15,3 nM; diazepam, 43,2 nM; y clorodiazepóxido, 7,4 micronM, valores que se correlacionaron significativamente con los correspondientes valores determinados por otro método. Los valores de concentración correspondientes a benzodiazepinas no identificadas, extraídas de sangre, fueron expresados en equivalentes de diazepam. La sensibilidad para diazepam fue 3,3 nM, y los niveles de dosis entre 15 y 138 nM, mostraron valores de coeficiente de variación intra e inter ensayo, variando desde 3,4 a 12,2%, y desde 13 a 30,7%, respectivamente

Benzodiazepinas: efeito clínico, correlacionado ao nível plasmatico (Cp) / Benzodiazepines: clinical effect, related to plasma level

A correlaçäo entre os níveis plasmáticos de BZ e seus diversos efeitos é elucidada com ênfase no metabolismo, farmacocinética, fenômeno dos receptores, validade dos métodos de análise utilizados e parâmetros para eficácia. Acredita-se que: 1) a farmacocinética da BZ e seus metabólitos ativos; 2) as características do receptor de BZ1 e BZ2; 3) a integraçäo entre as vias neuronais GABA-érgica, alfa - e ß - adrenérgica e 5-HT-érgica; 4) a regulaçäo superior ou inferior dos receptores de BZ; e 5) o tempo de ocupaçäo do receptor, todos contribuem para um modelo täo complexo que a previsäo absoluta dos efeitos de relaxamento muscular, anticonvulsivo, hipnótico, sedativo e ansiolítico ou da funçäo psicomotora comprometida dos níveis plasmáticos de BZ se torna muito difícil