Determination of salbutamol in human plasma and urine using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study

A sensitive and selective liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) was developed and validated for the determination of salbutamol in human plasma and urine, and successfully applied to the pharmacokinetic study of salbutamol in Chinese healthy volunteers after inhalation of salbutamol sulfate aerosol. Salbutamol and the internal standard (IS) acetaminophen in plasma and urine were extracted with ethyl acetate, separated on a C₁₈ reversed‐phase column, eluted with mobile phase of acetonitrile–ammonium acetate (5 m m ; 30:70, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi‐reaction monitoring mode using precursor → product ions of m/z 240.2 → 148.1 for salbutamol and 152 → 110 for the IS. The lower limits of quantitation of salbutamol in human plasma and urine by this method were 0.02 and 1 ng/mL, respectively. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and several stabilities were validated for salbutamol in human plasma and urine. In conclusion, the validation results showed that this method is robust, specific and sensitive, and can successfully fulfill the requirement of clinical pharmacokinetic study of salbutamol in healthy Chinese volunteers. Copyright © 2011 John Wiley & Sons, Ltd.     

Chemo- and regioselective assembly of polysubstituted pyridines and isoquinolines from isocyanides, arynes, and terminal alkynes

We have disclosed a general and efficient synthetic strategy for polysubstituted pyridines and isoquinolines with high chemo- and regioselectivity. In this methodology, 1-alkynyl imines act as the key compound to undergo a sequential alkynyl imine-allenyl imine isomerization/aza-Diels-Alder reaction/aromatization. In the first place, 1-alkynyl imines were formed in situ by a highly selective multicomponent reaction of isocyanides, arynes, and terminal alkynes and reacted with another molecule of arynes or terminal alkynes to furnish target heterocyclic products in a highly efficient and atom-economic manner. On the other hand, we attempted to prepare 1-alkynyl imines by other approaches to undergo a similar reaction sequence to afford polysubstituted pyridines and isoquinolines with a wider range. Different from the first approach, the second approach utilized the preprepared 1-alkynyl imines to introduce the related different substitutents into the final products: arynes or terminal alkynes bearing substituents different from those of 1-alkynyl imines have been successfully applied for the synthesis a wide variety of pyridines and isoquinolines with diversity.     

Gold nanoparticles assembling on smooth silver spheres for surface-enhanced Raman spectroscopy

A simple and cost-effective chemical method was introduced to assemble gold (Au) nanoparticles on smooth silver (Ag) spheres for realizing surface-enhanced Raman scattering (SERS) enhancement by the replacement reaction between chloroauric acid and Ag spheres. In addition, the Ag-Au core-shell spheres were fabricated when a certain amount of chloroauric acid was used in the reaction solution. We found that the Ag particles decorated with small Au nanoparticles demonstrated the strongest SERS enhancement, while Ag-Au core-shell spheres showed the weakest enhancement.     

Metabolite identification of tanshinol borneol ester in rats by high‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight mass spectrometry

Tanshinol borneol ester (DBZ) is a potential drug candidate composed of danshensu and borneol. It shows anti‐ischemic and anti‐atherosclerosis activity. However, little is known about its metabolism in vivo. This research aimed to elucidate the metabolic profile of DBZ through analyzing its metabolites using high‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight mass spectrometry. Chromatographic separation was performed on an Agilent TC‐C₁₈ column (150 × 4.6 mm, 5.0 μm) with gradient elution using methanol and water containing 0.2% (v/v) formic acid as the mobile phase. Metabolite identification involved analyzing the retention behaviors, changes in molecular weights and MS/MS fragment patterns of DBZ and its metabolites. As a result, 20 potential metabolites were detected and tentatively identified in rat plasma, urine and feces after administration of DBZ. DBZ could be metabolized to O‐methylated DBZ, DBZ‐O‐glucuronide, O‐methylated DBZ‐O‐glucuronide, hydroxylated DBZ and danshensu. Danshensu, a hydrolysis product of DBZ, could further be transformed into 12 metabolites. The proposed method was confirmed to be a reliable and sensitive alternative for characterizing metabolic pathways of DBZ and providing valuable information on its druggability.     

超高效液相色谱-四极杆/静电场轨道阱高分辨质谱对粮谷产品中20种真菌毒素的快速筛查和确证

建立了超高效液相色谱-四极杆/静电场轨道阱高分辨质谱快速筛查和确证粮谷产品中20种真菌毒素的方法。样品经乙腈（含2%（体积分数）甲酸）提取,用Captiva EMR-Lipid小柱净化,采用Thermo Hypersil Gold C₁₈柱（100 mm×2.1 mm,1.9 μm）分离,用四极杆/静电场轨道阱高分辨质谱进行分析。在全扫描模式下以分析物的保留时间和一级母离子信息实现快速筛查,以自动触发采集的二级碎片离子信息进行确证。结果显示,目标分析物在各自的质量浓度范围内线性关系良好（相关系数r²>0.99）,方法检出限为0.25~20 μg/kg,回收率为72.9%~117.8%,相对标准偏差为2.9%~15.2%（n=6）。该方法灵敏度高,结果准确、可靠,适用于粮谷产品中20种真菌毒素的快速筛查和确证。     

中药微量元素含量区间尺最佳分级问题的探讨

在深入研究中药微量元素含量区间尺的基础上，从统计学角度对区间尺的最佳分级问题作了详细探讨，提出用5级区间尺来衡量中药中不同元素含量间相对高低水平，理论上更合理。     

Fragmentation patterns of novel dithiocarbamate derivatives with pharmaceutical activity under electrospray ionization tandem mass spectrometry conditions

The fragmentation patterns of a novel series of dithiocarbamate derivatives with pharmaceutical activity were investigated by positive ion electrospray ionization mass spectrometry in conjunction with tandem mass spectrometry (ESI-MS(n)). In the gas phase, the dithiocarbamate protonated molecules containing the piperazinium moiety undergo losses of bromide to form the piperazinium cation by ionization, followed by subsequent losses of methyl bromide, ring opening and rearrangement of piperazinium. Furthermore, the dithiocarbamate derivatives and their intermediates both undergo cleavage of the C-S bond to produce two common fragment ions. The different fragmentation observed for these compounds facilitated their identification and could be valuable in the further study of their metabolic pathways as prodrugs.     

Synthesis of fluorescent dendritic 8-hydroxyquinoline ligands and investigation on their coordinated Zn(II) complexes

A series of luminescent PAMAM dendrons emanating from 8-hydroxyquinoline have been synthesized and their coordination with Zn(II) was investigated for the first time. The obtained dendritic Zn(II) complexes were soluble in common organic solvents. It was found that the luminescence intensity of G2 dendron 6 was higher than that of G1 dendron 4. Furthermore, when they were coordinated with Zn(II), red-shift was observed and the intensities of the coordinated Zn(II) complexes were higher than that of the corresponding ligands.