超高效液相色谱-串联质谱法测定动物组织中的金刚烷胺、金刚乙胺和盐酸美金刚

目的建立超高效液相色谱-串联三重四极杆质谱法(ultra performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)测定动物组织中金刚烷胺、金刚乙胺和盐酸美金刚的分析方法。方法样品经0.5%乙酸乙腈提取,经过PCX固相萃取小柱净化,以甲醇-含有0.1%甲酸的5 mmol/L乙酸铵水溶液为流动相,经Agilent Eclipse Plus C18 RRHD色谱柱,进行梯度洗脱分离,采用ESI正模式电离,多反应监测(multiple reaction monitoring,MRM)模式进行检测,以保留时间和定性离子对的相对丰度比定性,内标法定量。结果 3种金刚烷胺类药物的检出限(limits of detection,LODs,S/N=3)和定量限(limits of quantitation,LOQs,S/N=10)分别为0.1μg/kg和0.2μg/kg,在0.2~10 ng/m L浓度范围内,线性关系良好(r20.999),加标回收率为70.2%~82.7%,相对标准偏差为3.9%~6.4%。结论本方法操作简单、重现性好、背景噪音低、具有较高的灵敏度和选择性。     

同位素稀释-超高效液相色谱-串联质谱法测定禽类食品中利巴韦林和金刚烷胺类化合物残留量

目的建立同位素稀释-超高效液相色谱-串联质谱(UPLC-MS/MS)法检测禽类食品中利巴韦林和金刚烷胺类化合物(金刚烷胺、金刚烷甲胺、金刚烷乙胺、3,5-二甲基金刚胺)的残留量。方法样品经酶解,三氯乙酸沉淀蛋白,低温高速离心,上清液调节pH值后经PBA/PCX复合固相萃取柱净化,Agilent ZORBAX SB-Aq柱(3.0 mm×100 mm,1.8μm)分析利巴韦林,Waters BEH C_(18)色谱柱(2.1 mm×100 mm,1.7μm)分析金刚烷胺类化合物,串联质谱测定,同位素内标法定量。结果利巴韦林在1.0～100 ng/mL、金刚烷胺类化合物在0.2～20 ng/mL范围内呈良好的线性关系,相关系数(r)均为0.999。利巴韦林的检出限和定量限分别为0.5和1.5μg/kg;金刚烷胺类化合物的检出限和定量限分别为0.1和0.3μg/kg。利巴韦林(1.5～15μg/kg)和金刚烷胺类化合物(0.3～3.0μg/kg)添加3个浓度的检测结果显示,利巴韦林的回收率为91.4%～103.7%,金刚烷胺类化合物的回收率为94.3%～108.2%,相对标准偏差(RSD)均小于10%。结论本方法具有简便快捷、灵敏度高、定性准确等特点。     

Determination of adamantane derivatives in pharmaceutical formulations by using spectrophotometric UV-Vis method

A simple and sensitive extractive spectrophotometric method have been developed and validated for determination of amantadine hydrochloride (AM), memantine hydrochloride (MM) and rimantadine hydrochloride (RM) in pure and pharmaceutical formulations. The method is based on the reaction of these active compounds with bromophenol blue (BB) in acetate buffer (0.1 M) pH 3.5 to form an orange-colored products which have absorption maxima at 408 nm. The procedure of complexation was optimized with regard to such factors as concentrations of BB, pH of medium, a kind of extracting solvents and a number of extractions. Under the optimum conditions, linear relationships A₄₀₈ = f(c) with good correlation coefficients (≥0.996) and low limit of detection were obtained in the ranges of 50.0–220.0 µg·mL^?1, 20.0–150.0 µg·mL^?1 or 10.0–110.0 µg·mL^?1 for AM, MM and RM, respectively, for the spectrophotometric methods. The proposed method could be applied to the determination of AM, MM and RM in dosage forms. The recovery was 95.3–101.9%. The method was linear, precise and accurate.     

Self-Assembly of Diamondoid Molecules and Derivatives (MD Simulations and DFT Calculations)

We report self-assembly and phase transition behavior of lower diamondoid molecules and their primary derivatives using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. Two lower diamondoids (adamantane and diamantane), three adamantane derivatives (amantadine, memantine and rimantadine) and two artificial molecules (ADM•Na and DIM•Na) are studied separately in 125-molecule simulation systems. We performed DFT calculations to optimize their molecular geometries and obtained atomic electronic charges for the corresponding MD simulation, by which we predicted self-assembly structures and simulation trajectories for the seven different diamondoids and derivatives. Our radial distribution function and structure factor studies showed clear phase transitions and self-assemblies for the seven diamondoids and derivatives.     

液相色谱-串联质谱法测定动物组织中金刚烷胺和金刚乙胺的残留量

采用液相色谱-电喷雾串联质谱（LC-ESI-MS/MS）,在多反应监测（MRM）模式下建立了动物组织中金刚烷胺和金刚乙胺的检测方法。试样中的金刚烷胺和金刚乙胺经V(乙腈)∶V(1.0%三氯乙酸)=50∶50的混合溶液超声提取,混合阳离子交换柱净化,氮气吹干后,用1 mL V（甲醇）∶V（0.2%甲酸）=10∶90的溶液溶解残渣,液相色谱 串联质谱法测定,色谱保留时间和质谱碎片离子丰度比定性,外标法定量。该方法测得在鸡肉、鸡肝、猪肉、猪肝等动物组织中,金刚烷胺和金刚乙胺的检出限（LOD）均为0.4 μg/kg,定量限（LOQ）均为1.0 μg/kg;在0.5~100.0 μg/L线性范围内,相关系数r₂均大于0.999。添加回收率实验表明,以上4种动物组织中添加水平为1.0~100 μg/kg时,金刚烷胺和金刚乙胺的平均回收率在70.7%~92.3%之间,相对标准偏差为1.7%~11.7%。     

液相色谱-串联质谱法检测中兽药中金刚烷胺和金刚乙胺含量的不确定度评估

目的 评估液相色谱-串联质谱法检测中兽药中金刚烷胺和金刚乙胺含量的不确定度。方法 根据JJF 1059.1-2012《测量不确定度评定与表示》的相关规定, 对液相色谱-串联质谱法检测中兽药(白头翁散、苍术香连散、银翘散)中金刚烷胺和金刚乙胺含量测定的不确定度进行评定。结果 中兽药中金刚烷胺和金刚乙胺的含量分别为1.024 mg/kg、1.056 mg/kg时, 取k=2, 测定结果的相对扩展不确定度分别为0.07463、 0.07245 mg/kg, 结果分别表示为(1.024±0.07463)、(1.056±0.07245) mg/kg。结论 影响测量结果的不确定度主要来源为液相色谱-串联质谱仪的灵敏度、天平的精密度、操作的规范性。