高效液相色谱-串联质谱法测定盐酸二甲双胍及其制剂中痕量N -亚硝基二甲胺

建立了高效液相色谱-串联质谱（HPLC-MS/MS）检测盐酸二甲双胍原料和制剂中N -亚硝基二甲胺（NDMA）含量的方法。样品以水为提取溶剂,经涡旋混匀、恒温振荡、高速离心、微孔过滤后进行HPLC-MS/MS分析。采用ACE EXCEL 3 C18-AR色谱柱（150 mm×4.6 mm,3 μm）分离,流动相为均含0.1%甲酸的水和甲醇溶液,梯度洗脱,流速0.8 mL/min,柱温40℃,自动进样器温度10℃。采用阀切换技术保护质谱仪,设置六通阀切换使保留时间2.85~7.00 min的流动相进入质谱,其余时间流动相进入废液。质谱部分采用大气压化学电离（APCI）源,在正离子、MRM模式下扫描,雾化器流量为3 L/min,加热器流量为10 L/min,接口温度为300℃,脱溶剂管温度为250℃,加热块温度为400℃,干燥器流量为10 L/min。NDMA定量离子对为m /z 75.0→43.1,碰撞能量（CE）为-17.0 eV,定性离子对为m /z 75.0→58.2,CE为-16.0 eV。采用外标法定量。对方法进行了详细的方法学验证,结果表明,该法专属性良好,溶剂和辅料对NDMA测定无干扰。NDMA峰面积与其质量浓度在1.00~100.00 ng/mL范围内呈现良好的线性关系,相关系数（r ）>0.9999;低、中、高3个水平下NDMA的回收率为94.55%~114.67%,RSD为4.73%~13.46%;检出限和定量限分别为0.20 ng/mL和1.00 ng/mL;NDMA在自动进样器放置0、8、24 h的峰面积RSD为2.08%。使用该方法对113批盐酸二甲双胍原料和制剂供试品中的NDMA进行测定,发现原料药中NDMA检出量不超限,但有8批二甲双胍制剂超过了限度。该法灵敏、准确,操作简便,可用于盐酸二甲双胍原料及制剂中的NDMA检测。     

LC-MS/MS法快速测定吡罗昔康制剂中吡罗昔康含量

建立了快速液相色谱-质谱/质谱联用法测定吡罗昔康制剂中吡罗昔康含量的方法。样品以0.1 mol/L盐酸甲醇溶液提取、微孔滤膜过滤、离心后,通过电喷雾离子化(ESI),采用多反应检测(MRM)方式进行正离子检测,用于定量分析的检测离子为m/z 332.2→94.8。采用Shim-pack XR-ODS(3.0 mm×75mm,2.0μm)柱分离,以乙腈-水-甲酸(60:40:0.1,V/V/V)为流动相,流速为0.40 mL/min,在3 min内完成吡罗昔康定量分析。线性范围为2.5～1000.0ng/mL,最低检测限为2.5 ng/mL;日内测定的相对标准偏差小于3.2%,日间测定的相对标准偏差小于3.8%。方法可作为吡罗昔康制剂的质量中吡罗昔康控制方法,并可用于少量血浆样品的测定,也适用于药物代谢动力学研究。     

尿液中新型合成大麻素及其代谢物的检验研究

利用液相色谱-高分辨质谱（LC-HRMS）建立了尿液中3种新型合成大麻素及5种代谢物的快速检验方法。前处理分别采用沉淀蛋白和固相萃取2种方法,选用Thermo Hypersil GOLD C18(100 mm×2.1 mm,1.9μm)色谱柱进行分离,以含10 mmol/L甲酸铵的0.1%甲酸水溶液和含0.1%甲酸的甲醇溶液进行梯度洗脱;采用正离子扫描模式,一级质谱全扫描/数据依赖二级质谱扫描（Full MS/dd-MS2）进行检测。结果表明,沉淀蛋白法检出限为1～3 ng/mL,定量限为2～5 ng/mL,固相萃取法检出限为0.1～1 ng/mL,定量限为0.5～2 ng/mL,回收率为76.5%～91.7%,基质效应范围为77.6%～97.3%,日内日间相对标准偏差均小于12%。将建立的方法用于检验疑似合成大麻素吸食者的尿液检材并检出了目标物,表明所建立的方法可应用于公安机关对实际案件的检验。     

超高效液相色谱-串联质谱法测定鸡肉中头孢拉定残留

建立测定鸡肉中头孢拉定残留的超高效液相色谱-串联质谱分析方法。鸡肉样品经80%乙腈水溶液提取,PRiME HLB柱固相萃取净化,0.2%甲酸水溶液稀释,采用Waters ACQUITY UPLC HSS T3色谱柱(100 mm×2.1 mm,1.8μm)分离,以0.1%甲酸-0.1%甲酸乙腈为流动相,梯度洗脱,基质加标外标法定量。实验结果表明,头孢拉定在0.5～50.0 ng/mL浓度范围内呈良好的线性关系(R~2=0.9998),定量限为1μg/kg。向空白鸡肉中添加头孢拉定含量为1.00μg/kg、2.00μg/kg、10.0μg/kg时,回收率在77.3%～106.8%之间,相对标准偏差在3.2%～10.5%之间。本方法操作简便、快捷,实验结果准确、稳定,可满足鸡肉中头孢拉定残留量的检测。     

液相色谱-串联质谱法同时测定人血清中皮质酮与皮质醇

建立了同时测定人血清中皮质酮和皮质醇的液相色谱-串联质谱法。血清经正己烷除脂净化、叔丁基甲醚提取后,以乙腈-0.1%甲酸溶液(含0.01 mol/L甲酸铵)为流动相,流速为0.3 mL/min。用Agilent E-clipse Plus-C18色谱柱(150 mm×2.1 mm,3.5μm)分离,正离子模式下进行串联质谱检测。皮质酮和皮质醇浓度在0.5～200 ng/mL范围内线性关系良好,相关系数(r2)分别为0.999 7、0.999 4。皮质酮和皮质醇分别在5.0、25.0、75.0 ng/mL和0.5、2.5、10.0 ng/mL 3个加标水平下的平均回收率为86.6%～102.7%,相对标准偏差不大于7.1%,检出限分别为0.1 ng/mL和0.05 ng/mL。该方法操作简便、灵敏度高、重现性好、定性定量准确,适用于同时测定血清中的内皮质酮和皮质醇。     

超高效液相色谱-串联质谱法同时测定蜂蜜中硝基咪唑类、磺胺类、喹诺酮类兽药残留

建立蜂蜜样品中硝基咪唑类、磺胺类、喹诺酮类共36种兽药残留的固相萃取-超高效液相色谱-串联质谱检测方法。蜂蜜样品用H3PO4溶液(体积分数0.1%)溶解后,过滤,用Oasis HLB和PSA固相萃取柱净化,外标法定量。测定时用Eclipse Plus C18色谱柱(100 mm×2.1 mm,1.8μm)分离,乙腈-甲醇-甲酸溶液梯度洗脱,质谱测定采用多反应监测(MRM)模式。36种兽药的检出限在0.4～4.0 ng/mL,回收率在63.2%～125.5%,相对标准偏差均低于22%。     

超高效液相色谱串联质谱法同时快速检验全血中扎来普隆及其代谢产物

建立了全血中扎来普隆及其代谢产物5-氧扎来普隆和脱乙基扎来普隆超高效液相色谱-三重四级杆质谱(UPLC-TQ/MS)快速检验方法.采用改良后的QuEChERS前处理方法,全血样品用0.1％甲酸-乙腈提取,经无水MgSO4脱水净化,Waters BEH C18色谱柱分离,0.1％甲酸和0.1％甲酸-乙腈进行梯度洗脱.采用电喷雾电离,正离子(ESI+)模式扫描,多反应监测(MRM)模式检测.扎来普隆及其代谢产物在0.5～100 ng/mL范围内线性关系良好(R2≥0.997),回收率为92.0％～100.1％,相对标准偏差为1.9％ ～5.3％,方法检出限(S/N=3)均为0.05 ng/mL,定量限(S/N=I0)在0.1～0.5 ng/ mL范围内.     

HPLC-MS/MS同时检测人血液中佐匹克隆、唑吡坦、扎来普隆和褪黑素

建立液相色谱串联质谱同时检测全血中佐匹克隆、唑吡坦、扎来普隆和褪黑素的方法。采用液液萃取进行提取,提取物以Inersil ODS(2.1×100 mm,3.5μm)色谱柱分离,以10 mmol/L的甲酸铵水溶液(体积分数0.1%甲酸)-乙腈(体积分数0.1%甲酸)为流动相梯度洗脱,流速为0.3 m L/min,液相色谱串联质谱检测。全血中佐匹克隆、唑吡坦和褪黑素的线性范围为0.20~100.0ng/m L,检出限为0.20ng/m L;扎来普隆的线性范围为0.50~100.0ng/m L,检出限0.50ng/m L。     

高效液相色谱-四极杆/飞行时间高分辨质谱测定化妆品中的西咪替丁及雷尼替丁

建立了化妆品中西咪替丁及雷尼替丁的高效液相色谱-四极杆/飞行时间高分辨质谱检测方法,并对其质谱裂解规律进行研究。待测样品经甲醇超声提取,过滤膜后经Zorbax SB-Aq色谱柱(3.0 mm×100 mm,1.8μm)分离,用乙腈-含0.1%甲酸的水溶液梯度洗脱后,在双喷雾电喷雾离子源正离子模式下检测,数据采集使用一级母离子全扫描和目标二级离子扫描。在不同的化妆品基质中,西咪替丁和雷尼替丁分别在5.65～113 ng/mL和4.95～99.0 ng/mL范围内线性关系良好(r0.999),检出限分别为1.1、0.99 ng/mL,定量下限分别为5.6、5.0 ng/mL;2种待测物在低、中、高3个加标水平下的回收率为86.7%～110%,相对标准偏差(RSD)为0.90%～6.0%,方法重复性良好(RSD10%)。该方法前处理简单,灵敏度较好,线性、回收率及重复性均满足方法学要求,可用于化妆品中西咪替丁和雷尼替丁的筛查测定。     

固相萃取-液相色谱串联质谱法测定城市污水中他莫昔芬和来曲唑

他莫昔芬和来曲唑常用于治疗雌激素依赖型乳腺癌。本研究建立了城市污水中他莫昔芬和来曲唑的超高效液相色谱-串联质谱(UPLC-MS/MS)联用检测方法。水样通过Oasis HLB固相萃取柱富集后串联氨基柱,先用6 mL甲醇洗脱,再用3 mL甲醇洗脱氨基柱,合并洗脱液后浓缩。使用ACQUITY UPLCTM BEH C18反相柱,流动相为0.1%甲酸-乙腈,在梯度条件下分离;目标分析物使用超高效液相色谱-电喷雾串联质谱进行测定。本方法对他莫昔芬和来曲唑的线性范围分别是1.0～100μg/L和0.1～100μg/L,相关系数R2>0.997,检出限分别为1.0和0.1 ng/L,进水和出水的3个不同水平的加标平均回收率为68.8%～103.0%,相对标准偏差小于15%。本方法可用于城市污水中相关物质的分析。     

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.     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

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.     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.