液相色谱-串联质谱同时测定禽肉组织中盐酸金刚烷胺、盐酸金刚乙胺、地塞米松、替米考星及喹乙醇代谢物的残留量

建立了同时测定禽肉组织中盐酸金刚烷胺、盐酸金刚乙胺、地塞米松、替米考星及喹乙醇代谢物残留量的液相色谱-串联质谱分析方法。样品用2 mol/L氢氧化钠溶液水解,盐酸调节p H值后,以乙腈作为提取溶剂,经C18固相萃取柱净化。各待测物分别经0.1%甲酸甲醇溶液和氨化甲醇(0.1%氨水)洗脱,Phenomenex Kinetex C18(100 mm×4.6 mm,2.6μm)色谱柱进行分离,采用0.1%甲酸(含5 mmol/L乙酸铵)-甲醇作流动相,梯度洗脱,串联质谱法对5种药物含量进行测定。结果表明,5种药物在2~100μg/L范围内线性关系良好,相关系数为0.996 2~0.999 8。在加标浓度为5~50μg/kg的禽肉组织中,这5种药物的加标回收率为73.7%~92.3%,相对标准偏差(n=5)为3.9%~16.6%,检出限为0.2~3.0μg/kg,定量下限为0.7~10μg/kg。方法快速、简便、经济实用,符合法规要求,可满足日常检测的需要。     

分散固相萃取净化-超高效液相色谱-串联质谱法测定鸡蛋和鸡肉中金刚烷胺和金刚乙胺残留

建立了鸡蛋和鸡肉中金刚烷胺和金刚乙胺残留量的分散固相萃取-超高效液相色谱-串联质谱测定方法。鸡蛋和鸡肉样品经氨水-乙腈(2 : 98, v/v)提取后,提取液经氮气吹干至1 mL后,利用C18和NH₂填料进行分散固相萃取净化,过滤膜后分析。采用ZORBAX C18色谱柱分离,用1 mmol/L乙酸铵水溶液(含0.1%(v/v)甲酸)-甲醇作为流动相进行梯度洗脱,正离子多反应监测模式。结果表明,金刚烷胺和金刚乙胺在0.15~10.0 μ g/L范围内具有较好的线性关系,鸡蛋和鸡肉中的检出限均为0.05 μ g/kg,定量限均为0.20 μ g/kg。当2种药物在鸡蛋和鸡肉中的加标水平为0.2、1.0和2.0 μ g/kg时,平均回收率范围为89%~108%,相对标准偏差范围为5.0%~8.6%。该方法能够满足鸡蛋和鸡肉中金刚烷胺和金刚乙胺残留量分析的要求。     

盐酸金刚乙胺的合成

盐酸金刚乙胺(1)是一种抗病毒和镇静药物,主要用于预防和治疗Ａ型流感病毒感染[1]。文献[2,3]以溴代金刚烷(3)为原料,在浓硫酸存在下与乙炔气体反应,然后水解得到中间体1 金刚烷甲基酮(7),且产物需经过柱分离,总收率40%。本文参考文献[4,5],按如下路线合成了标题化合物。1　实验部分1.1　主要仪器和试剂ＩＲ(60ＳＸＲ ＦＴＩＲ);1Ｈ ＮＭＲ(ＦＸ 90Ｑ);ＭＳ(ＭＡＴ 2000)。熔点用毛细管法测定,温度计未经校正。金刚烷(工业品)98%;浓硫酸(工业品)98 4%;其它试剂为化学纯。1.2　合成1 溴代金刚烷(3)　在烧瓶中,依次加入2(320ｇ,2.35ｍｏｌ…     

Syntheses and crystal structures of three copper(II) complexes with bulky Schiff bases derived from rimantadine

The reactions of copper(II) chloride dihydrate and three bulky Schiff base ligands derived from rimantadine and salicylaldehyde (or methoxy-substituted salicylaldehydes), generated C₃₈H₄₈CuN₂O₂ (1), C₄₀H₅₂CuN₂O₄ (2), and C₄₀H₅₂CuN₂O₄ (3), respectively. These complexes were characterized by infrared spectra, UV–vis, elemental analysis and molar conductance. X-ray single-crystal diffraction analysis reveals that 1 has two different spatial configurations, 1a and 1b. For 1a, each asymmetric unit consists of one mononuclear copper(II) molecule. For 1b, each asymmetric unit consists of two copper(II) mononuclear molecules. All the complexes crystallize in the monoclinic system, P2₁/c space group for 1a and 2; P2₁/n space group for 1b; C2/c space group for 3. Each complex for 1–3 consists of one copper(II) and two corresponding deprotonated ligands. The central copper(II) in all complexes is four-coordinate via two nitrogens and two oxygens from the corresponding Schiff base ligands. The geometry around copper in 1a, 1b, and 2 is distorted square planar, but square planar in 3.     

毛细管气相色谱法测定复方盐酸金刚乙胺胶囊中的盐酸金刚乙胺

复方盐酸金刚乙胺胶囊为一新的复方制剂,其主要成分为盐酸金刚乙胺、对乙酰氨基酚、盐酸伪麻黄碱和马来酸氯苯那敏,国内外均未上市,其生产工艺及处方正在申请专利。盐酸金刚乙胺是盐酸金刚烷胺的类似物,抗A型流感病毒活性比后者强,而中枢神经毒性比后者小。本文以盐酸金刚烷胺为内标,对样品先碱化后提取,然后采用气相色谱法（GC）测定其中的盐酸金刚乙胺含量。     

Simultaneous determination of amantadine and rimantadine by HPLC in rat plasma with pre-column derivatization and fluorescence detection for pharmacokinetic studies

We investigated simultaneous high-performance liquid chromatographic (HPLC) determination of amantadine hydrochloride (AMA) and rimantadine hydrochloride (RIM) levels in rat plasma after fluorescent derivatization with o-phthalaldehyde and 2-mercaptoethanol. Afterwards, the method was applied to determine their pharmacokinetics. The retention times of AMA and RIM derivatives were 12.6 and 22.2 min and the lower limits of detection were 0.025 and 0.016 microg/mL, respectively. The coefficients of variation for intra- and inter-day assay of AMA and RIM were less than 5.1 and 7.6%, respectively. After i.v. administration of AMA or RIM to rats, the total body clearance and distribution volume at the steady-state of RIM were higher than those of AMA. Bioavailability of AMA and RIM was 34.9 and 37.2%, respectively. When AMA and RIM were p.o. co-administered, the area under the plasma concentration--time curve of RIM was significantly lower than that after RIM alone. On the other hand, pharmacokinetic parameters of AMA did not significantly change. These results indicate that our HPLC assay is simple, rapid, sensitive and reproducible for simultaneously determining AMA and RIM concentrations in rat plasma and is applicable to their pharmacokinetic studies. Also, co-administration of AMA and RIM may result in the lack of pharmacological effects of RIM.     

金刚乙胺水杨醛Schiff碱锌(Ⅱ)配合物的合成、表征、晶体结构和热分解动力学研究

A Zinc(Ⅱ) complex [ZnCl₂(HL)₂] with Schiff base HL derived from rimantadine and salicylaldehyde was synthesized and characterized by elemental analysis, infrared spectra, ¹H NMR spectra,molar conductance, ultraviolet and visible spectra, thermal analysis. Its structure was determined by single crystal X-ray diffraction method. The complex, C₃₈H₅₀Cl₂N₂O₂Zn, crystallizes in the orthorhombic system, space group Aba2 with a=1.381 7(3), b=2.275 0(5), c=1.145 0(2) nm, V=3.599(1) nm³, Z=4, M_r=653.79, F(000)=1 496, D_c=1.301 kg·m^-3, μ(Mo Kα)=0.866 mm^-1. The kinetic parameters were obtained from the analysis of TG curve by integral methods. The functions of thermal decomposition reaction mechanism are: F(α)=[1-(1-α)^1/3]², and kinetic compensation effect equation lnA=0.019 1E-0.142 7. CCDC: 253297.     

Trace analysis of rimantadine in human urine after dispersive liquid liquid microextraction followed by liquid chromatography–post column derivatization

The first dispersive liquid liquid microextraction scheme followed by liquid chromatography‐post column derivatization for the determination of the antiviral drug rimantadine in urine samples is demonstrated. The effect of the type and volume of organic extraction solvent, type and volume of disperser solvent, sample pH, ionic strength, extraction time, and centrifugation speed on the extraction efficiency were studied. Rimantadine and the internal standard (amantadine) were chromatographed using a reversed phase monolithic stationary phase with a mixture of equal volumes of methanol and phosphate buffer (pH = 3) as mobile phase. On‐line post‐column derivatization of the analyte was performed using a “two‐stream” manifold with o‐phthalaldehyde and N‐acetyl‐cysteine at alkaline medium. Under the optimized extraction conditions, the enrichment factor of rimantadine was 58. The linear range was 5–100 µg/L with correlation coefficient r of 0.9984 while the limit of detection achieved was 0.5 µg/L. The within‐day and between‐day precision for the tested concentration levels were less than 14.3% and the mean recoveries obtained from the spiked samples were ranged between 87.5 and 113.9%. The main advantages of the proposed method are the simplicity of operation, rapidity, low cost, and low limit of detection of the analyte.