高效液相色谱-四极杆/线性离子阱质谱法同时测定艾司奥美拉唑钠中2种潜在基因毒性杂质残留

建立了高效液相色谱-四极杆/线性离子阱质谱法(HPLC-QTRAP-MS/MS)同时测定艾司奥美拉唑钠中氮氧物(GTI E)和氮氧磺酰物(GTI I) 2种潜在基因毒性杂质痕量残留的分析方法。艾司奥美拉唑钠药物以30%(体积分数)乙腈水溶液溶解后,采用Agela VenusiL MP-C_(18)色谱柱(2.1 mm×100 mm,3μm)分离,以乙腈-水为流动相梯度洗脱,在流速0.2 mL/min,柱温35℃,进样量1μL,电喷雾负离子(ESI~-)扫描方式下以多反应离子监测(MRM)模式进行检测。结果表明,艾司奥美拉唑钠潜在基因毒性杂质GTI E和GTI I分别在1.26～44.8、1.34～45.2μg/L范围内线性关系良好,相关系数(r)分别为0.994 7和0.992 8,检出限(S/N=3)分别为0.381、0.384μg/L,定量下限分别为1.26、1.34μg/L,平均加标回收率分别为86.3%～87.6%和85.8%～91.4%,相对标准偏差(RSDs)分别为1.5%～2.2%和0.7%～4.0%。该方法操作简单、灵敏度高、重现性好,可用于艾司奥美拉唑钠药物中GTI E和GTI I 2种潜在基因毒性杂质的同时测定。     

液相色谱-串联质谱法测定吉非替尼中4种基因毒性杂质（英文）

建立了一种同时测定吉非替尼中4种基因毒性杂质3-氯-4-氟苯胺、3,4-二氟苯胺、3-氟-4-氯苯胺和3,4-二氯苯胺的高效液相色谱-串联质谱(HPLC-MS/MS)方法。用Inertsil ODS-3柱(100 mm×3.0 mm, 3μm)为色谱柱,以0.1%(体积分数,下同)甲酸水溶液-0.1%甲酸乙腈溶液为流动相,在电喷雾正离子模式下进行测定。该方法在特异性、线性、精密度、准确性、稳定性和耐用性方面得到了验证。4种基因毒性杂质在0.6～96.0μg/L范围内与峰面积呈良好线性关系。检测限和定量限分别为0.2～2.0μg/L和0.6～6.0μg/L。所有杂质的回收率为91.0%～98.5%。检测后,在批号16052301和R16052501-1样品中仅检测到3-氯-4-氟苯胺,但低于杂质限度(6 mg/L)。该方法简便可靠,可用于吉非替尼中4种基因毒性杂质的测定,并为质量控制提供参考。     

液相色谱-串联质谱法测定吉非替尼中4种基因毒性杂质

建立了一种同时测定吉非替尼中4种基因毒性杂质3-氯-4-氟苯胺、3,4-二氟苯胺、3-氟-4-氯苯胺和3,4-二氯苯胺的高效液相色谱-串联质谱（HPLC-MS/MS）方法。用Inertsil ODS-3柱（100 mm×3.0 mm,3μm）为色谱柱,以0.1%（体积分数,下同）甲酸水溶液-0.1%甲酸乙腈溶液为流动相,在电喷雾正离子模式下进行测定。该方法在特异性、线性、精密度、准确性、稳定性和耐用性方面得到了验证。4种基因毒性杂质在0.6~96.0μg/L范围内与峰面积呈良好线性关系。检测限和定量限分别为0.2~2.0μg/L和0.6~6.0μg/L。所有杂质的回收率为91.0%~98.5%。检测后,在批号16052301和R16052501-1样品中仅检测到3-氯-4-氟苯胺,但低于杂质限度（6 mg/L）。该方法简便可靠,可用于吉非替尼中4种基因毒性杂质的测定,并为质量控制提供参考。     

高效液相色谱-四极杆/线性离子阱质谱仪测定盐酸黄酮哌酯中的1-(2-羟乙基)哌啶残留

建立了盐酸黄酮哌酯中1-(2-羟乙基)哌啶的高效液相色谱-四极杆/线性离子阱质谱(HPLC-QTRAP-MS/MS)定量分析方法。盐酸黄酮哌酯药物用0.1%甲酸溶解后,经Agilent ZORBAX SB-Aq C_(18)(2.1 mm×100mm,1.8μm)色谱柱分离,以乙腈-0.1%甲酸水作为流动相进行梯度洗脱,采用电喷雾正离子扫描方式,以选择反应监测(SRM)模式进行检测。结果表明,1-(2-羟乙基)哌啶在10~100μg/L范围内线性关系良好(r=0.999 7),加标回收率为98.9%~106.8%,相对标准偏差(RSD)均不大于3.0%,方法检出限(S/N=3)为6.0mg/L,方法定量下限(S/N=10)为20 mg/L。该方法简单、灵敏、准确,适用于盐酸黄酮哌酯中1-(2-羟乙基)哌啶残留的测定。     

超高效液相色谱-串联质谱法测定食品中4种罂粟壳生物碱

建立了超高效液相色谱-串联质谱法(UPLC-MS/MS)测定食品中可卡因、可待因、吗啡、盐酸罂粟碱的检测方法.样品经氨化甲醇提取,采用Capcell Pak C_(18)(250 mm×2.0 mm,MGⅡ 5μm)色谱柱,以色谱纯乙腈为流动相A,以20 mmol/L乙酸铵和0.1%甲酸缓冲液为流动相B,进行梯度洗脱.在优选条件下,可待因、吗啡方法线性范围为5.0~50.0μg/L,可卡因、盐酸罂粟碱的方法线性范围为1.0~20.0μg/L,相关系数均大于0.999,方法检出限在0.1~0.8μg/kg之间,平均回收率为76.0%~111.2%,相对标准偏差RSD低于10%.     

禽蛋中头孢噻肟残留的高效液相色谱-串联质谱法测定

建立了高效液相色谱-串联质谱(LC-MS/MS)测定禽蛋中头孢噻肟药物残留的方法。禽蛋样品中的头孢噻肟用纯水提取,乙腈沉淀蛋白,Oasis HLB(500 mg,6 mL)固相萃取柱净化,8 mL甲醇洗脱。采用Zorbax XDB-C18(2.1 mm×50 mm,3.5μm)色谱柱,以0.2%甲酸水-乙腈为流动相,0.3 mL/min梯度洗脱,经高效液相色谱分离后,采用电喷雾质谱正离子模式电离,多反应选择离子检测(MRM)模式测定。检测离子对为m/z456.1/396.1、m/z456.1/324.1,其中m/z456.1/396.1为定量离子对。在1.35~135μg/L范围内标准曲线的线性关系良好,相关系数为0.999 3;在1.0、50.0、100μg/kg3个添加水平的平均加标回收率为87%~99%,相对标准偏差为1.9%~3.9%;方法检出限为0.3μg/kg,定量下限为1.0μg/kg。该方法简便、灵敏、准确、可靠,适用于禽蛋中头孢噻肟药物残留的分析。     

高效液相色谱-四极杆/线性离子阱质谱测定替米沙坦中N-甲基邻苯二胺残留量

建立了高效液相色谱-四极杆/线性离子阱质谱(HPLC-QTRAP-MS/MS)测定替米沙坦中N-甲基邻苯二胺残留量的分析方法。替米沙坦药物以水-乙腈(80∶20,体积比)溶解后,采用Agilent Eclipse XDB-C18色谱柱(3.5μm,2.1 mm×100 mm)进行分离,以0.1%(体积分数)甲酸水和乙腈作为流动相进行梯度洗脱,电喷雾正离子(ESI+)扫描方式下选择离子监测(SRM)模式对样品进行检测。结果表明,N-甲基邻苯二胺在2.0~50μg/L范围内线性关系良好(r0.99),检出限(S/N=3)为0.5μg/L,定量下限(S/N=10)为2.0μg/L。该方法操作简单、灵敏度高、重现性好,可用于替米沙坦中N-甲基邻苯二胺残留量的测定。     

QuEChERS-高效液相色谱-串联质谱法测定动物源食品中阿奇霉素残留

建立了QuEChERS前处理,液相色谱-串联质谱测定动物源食品中阿奇霉素残留的快速分析方法。样品以乙腈提取,N-丙基乙二胺(PSA)净化,采用Zorbax Eclipse Plus C18柱(3.0 mm×100 mm,1.8μm)分离,以乙腈-0.1%甲酸溶液为流动相,梯度洗脱。阿奇霉素采用电喷雾正离子源(ESI+)、多重反应监测(MRM)模式检测,以保留时间和特征离子对(母离子和2个碎片离子)信息比较进行定性分析和定量分析。阿奇霉素在1.0~50.0 ng/m L范围内线性相关系数均大于0.995;在6种基质(鸡肉、牛肉、猪肉、猪肝、鲤鱼、牛奶)中方法的检出限(S/N=3)均为0.3μg/kg,定量限(S/N=10)均为1.0μg/kg;3个加标水平(1,2,10μg/kg)下,回收率为81.4%~103.8%,相对标准偏差为3.6%~8.9%。     

凝胶渗透色谱/液相色谱串联质谱法测定畜禽及水产品组织中头孢喹肟的残留量

建立了牛肉、猪肉、鸡肉、鱼肉、泥鳅肉等动物组织中头孢喹肟残留的高效液相色谱串联质谱检测方法。样品经乙腈-水(体积比4∶1)提取、Sephadex LH-20凝胶柱(16 mm i.d.×320 mm)净化;采用CAP-CELL PAK MG C18(100 mm×2.0 mm,3μm)色谱柱,以0.1%甲酸-甲醇为流动相,0.2 mL/min梯度洗脱,电喷雾正离子模式电离,选择反应监测(SRM)模式测定。检测离子对为m/z 529.1/134.2、529.1/396.1、529.1/125.1,其中m/z 529.1/134.2为定量离子对。在优化实验条件下,头孢喹肟在5.0～200μg/L范围内线性良好,相关系数(r)为0.999 1,检出限(LOD)为1.0μg/kg,定量下限(LOQ)为3.0μg/kg;在3.0、10、50、100μg/kg 4个加标水平下的平均回收率为75%～105%,相对标准偏差(RSD)为2.4%～11.9%。该方法净化效果理想、重复性好、灵敏度高,可满足动物组织中头孢喹肟药物残留的检测要求。     

超高效液相色谱-串联质谱法测定鳗鱼肌肉组织中6种喹诺酮类药物残留

建立了快速测定鳗鱼肌肉中氧氟沙星、诺氟沙星、恩诺沙星、环丙沙星、氟甲喹和恶喹酸6种喹诺酮类(QNs)药物残留的超高效液相色谱-串联质谱(UPLC-MS/MS)方法。样品经0.2mol/L磷酸盐缓冲液(PBS,pH=7.0)匀浆后,采用酸性乙腈(含0.2%甲酸)提取,正己烷脱脂,用ACQUITY UPLC BHE C18柱(100×2.1 mm,1.7μm),以乙腈-5mmol/L乙酸铵溶液(含0.2%甲酸)为流动相,用多反应监测(MRM)正离子扫描方式进行质谱检测,内标法定量。结果表明,该方法对以上6种喹诺酮类药物的线性范围为0.1~50μg/kg,相关系数(r)均大于0.9976;检出限为0.03~0.25μg/kg,定量限为0.1~0.8μg/kg,在1.0、2.0、10μg/kg 3个添加水平的回收率为84.8%~97.8%,相对标准偏差为4.5%~11.3%。该法简单、灵敏、特异性强,适用于鳗鱼肌肉中喹诺酮类药物多残留的检测。     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Cu0-catalysed 1,3-dipolar cycloadditions of α-amino acid derived N,N-cyclic azomethine imines to ynones

A series of 20 CuAIAC reactions between eight 4-acylamino substituted pyrazolidine-3-one-1-azomethine imines and four terminal ynones were performed using Cu⁰ as catalyst. The corresponding fluorescent cycloadducts were obtained in very high yields upon simple workup. Thus, Cu-metal turned out to be a better catalyst than Cu^I in terms of yield and ease of isolation. Availability of azomethine imines, mild reaction conditions, and simple workup enable a “click” access to libraries of densely substituted 2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-ones. Reactivity of differently substituted dipoles was evaluated experimentally and by quantum chemical methods (DFT).     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.