Simultaneous determination of midazolam and 1'-hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

A sensitive and simple liquid chromatography-tandem mass spectrometry method for the determination of midazolam and 1'-hydroxymidazolam in human plasma has been developed and validated with a dynamic range of 0.1-250 ng/mL. The analysis was based on semi-automated liquid-liquid extraction followed by evaporation of the extraction solvent, reconstitution and chromatography on a reversed-phase C(18) column. The mobile phase consists of 5 mm ammonium acetate and methanol and runs in gradient at a flow rate of 0.25 mL/min with column temperature of approximately 20 degrees C. The entire column effluent was transferred into the LC-MS/MS interface operated in positive electrospray ionization mode. The chromatographic run time was 4.3 min per injection, with retention times for midazolam, 1'-hydroxymidazolaml and the internal standard, triazolam, of 2.5, 2.3 and 2.1 min, respectively. The intra-day and inter-day precision (RSD %) and accuracy (bias %) of the quality control samples were <15.0% and within +/-13%, respectively. The current method has been applied to a clinical drug-drug interaction study in human.     

吡唑三杂环化合物的制备表征及生物活性的研究

以1,3-二苯基-4-吡唑甲醛为原料, 合成中间体吡唑腙和吡唑基氨基硫脲, 进一步合成出一系列新颖的含有1,3,4-噁二唑, 1,2,4-三氮唑和1,3,4-噻二唑的吡唑三杂环的化合物, 通过抑菌圈法和营养肉汤法对所制备的化合物的抗菌活性进行了测试, 测试结果表明: 3-芳基-4-(1,3-二苯基-4-吡唑甲酰基)-1,2,4-三唑啉-5-硫酮对金黄色葡萄球菌具有良好的抗菌活性.     

Synthesis and Biological Activity Test of Some New Five Membered Heterocycles

A new series of 1,3,4‐oxadiazoles, 1,2,4‐triazoles, 1,3,4‐thiadiazoles were synthesized using alkylhydrazides as the starting materials, and then 1,2,4‐triazoles were used to synthesize [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles. All the compounds were evaluated for in vitro antibacterial activity and antitumor activity.     

气相色谱-微池电子捕获器检测尿液中的三唑仑

建立了气相色谱-微池电子捕获检测器(GC-μECD)检测尿液中三唑仑的方法。筛选了pH值、提取溶剂、涡旋时间,优化了液-液萃 取条件。在0.2～50 ng/mL范围内,线性关系良好,相关系数为0.9995;方法的检出限为0.1 ng/mL,日内和日间测定的相对标准偏差分 别为4.17%和5.31%,平均回收率为93.9%。该方法操作简便、灵敏度高、线性范围广、回收率高,完全能够满足日常检测工作的需要。     

气相色谱/质谱法测定猪肉中4种苯二氮(艹卓)类镇静剂残留

建立了同时测定猪肉中4种苯二氮类药物(地西泮、艾司唑仑、阿普唑仑、三唑仑)残留量的固相萃取气相色谱质谱方法。用乙腈提取药物,C18固相萃取柱净化,GC/MS分析。运用HP5毛细管柱(30m×0.25mm×0.25μm)进行分离,电子轰击电离源(EI)质谱选择离子模式(SIM)检测(地西泮m/z241、256、257、284;艾司唑仑m/z205、239、259、294;阿普唑仑m/z204、273、279、308;三唑仑m/z238、313、315、342),外标法定量(定量离子m/z分别为256、259、270和313)。4种苯二氮类药物的标准曲线线性回归系数均在0.99以上,地西泮线性范围超过5～100μg/L;回收率为60%～70%;相对标准偏差7.6%～12.9%,最低检出限为2μg/kg。艾司唑仑、阿普唑仑、三唑仑3种药物的线性范围超过50～1000μg/L;回收率为60%～115%;相对标准偏差3.8%～19.7%,检出限为10μg/kg。     

Specific and Sensitive High Performance Liquid Chromatographic Determination of Alprazolam or Triazolam

Abstract

A specific and highly sensitive liquid chromatographic procedure has been developed for the rapid determination of intact alprazolam or triazolam in dog serum, using these structurally similar triazolobenzodiazepines as mutual internal standards. The procedure consists of (1) extracting one ml of alkali buffered serum with toluene, (2) evaporating an aliquot of the toluene to dryness, and (3) quantitating the redissolved residue by HPLC using ultraviolet detection (221 nm). Samples were chromatographed on a microparticulate reverse phase column using a mobile phase composed of acetonitrile: isopropanol: water (94:5:1) and a flow rate of 0.75 ml/min. Metabolites of alprazolam and triazolam did not interfere in the assay. The lower limit of detection was approximately 1 ng/ml of serum extracted. The utility of the analytical methodology for the determination of alprazolam or triazolam in pharmacokinetic studies in the dog was demonstrated.