反相高效液相色谱法同时测定血清、尿液中尿酸、肌酐的含量

建立了同时测定人体血清、尿液中肌酐、尿酸含量的高效液相色谱分析方法。采用Hypersil ODS C18色谱柱,甲醇(A)-20 mmol/L乙酸铵(B)为流动相,梯度洗脱,流速1.0 mL/min,UV检测,检测波长235 nm。血清中肌酐、尿酸含量在2~20μg/mL范围内线性关系良好,尿液中肌酐、尿酸在5~1000μg/mL范围内线性关系良好;平均加标回收率在86.7%~99.0%,RSD小于5%。选择甲醇-乙酸铵作为流动相进行血清/尿液中肌酐、尿酸含量测定具有快速简便的特点,方法应用于健康人和糖尿病病人血清/尿液样本的测定,可以对临床病人进行快速监测。     

超高效液相色谱-串联质谱法快速测定人体尿液中4种巯基尿酸

1.00mL人体尿液样品经自制的萃取装置萃取后,收集萃取液,采用超高效液相色谱-串联质谱法快速测定萃取液中4种巯基尿酸的含量。以Waters Acquity UPLC~(TM) BEH C_(18)色谱柱为固定相,以不同体积比的0.05%(体积分数)乙酸溶液和甲醇的混合液为流动相进行梯度洗脱,串联质谱分析中采用电喷雾负离子源和多反应监测模式,采用内标法定量。4种巯基尿酸的检出限(3S/N)为0.012～0.082μg·L~(-1),测定下限(10S/N)为0.038～0.270μg·L~(-1)。方法用于人体尿液样品的分析,日内回收率为93.9%～102%,日内相对标准偏差(n=7)为2.0%～3.4%,日间回收率为93.4%～102%,日间相对标准偏差(n=7)为2.4%～4.1%。     

尿液中1,3-丁二烯代谢产物的液相色谱-串联质谱法检测

建立了人体尿液中1,3-丁二烯的代谢产物--丁烯醇巯基尿酸(MHBMA)和丁烯二醇巯基尿酸(DHBMA)的液相色谱-串联质谱(LC-MS/MS)检测方法.以DHBMA-D7、MHBMA-D6作内标,尿液酸化离心后采用反相固相萃取柱Isolute ENV+净化和富集.分析样品以无水甲醇和pH 2.5的0.1%甲酸水溶液为流动相,经Agilent Extend C18柱梯度洗脱,流速1 mL/min,柱后以三通分流,分流比约为3:1,柱温40 ℃.在多离子监测模式下进行定性和定量分析,采用负离子扫描模式.2种代谢物的精密度为1.02% ～7.79%,回收率为97% ～112%.用该方法同时测定了吸烟者和非吸烟者尿液中2种代谢物的平均质量浓度,结果表明,对于抽吸相同品牌相同支数的卷烟的吸烟者,由于吸烟行为和代谢途径不同,其尿中DHBMA和MHBMA的质量浓度存在着较大差异,而对于吸烟者尿液,其DHBMA、MHBMA的质量浓度分别是非吸烟者的5.1倍和9.1倍.因此,DHBMA和MHBMA有可能作为人体尿液中鉴别吸烟者和非吸烟者的生物标记物.     

超高效液相色谱-串联质谱法测定尿液中7种苯系物代谢物

建立了同时测定人体尿液中7种苯系物代谢物的超高效液相色谱-串联质谱检测方法。0.5 mL尿液经盐酸水解、EVOLUTE^?EXPRESS ABN固相萃取板(10 mg)净化、洗脱、稀释后测定。使用ACQUITY UPLC HSS T3色谱柱(100 mm×2.1 mm, 1.8μm),以0.1%甲酸水溶液和甲醇作为流动相进行梯度洗脱，分离目标化合物，负离子电喷雾多反应监测模式下测定含量。7种目标化合物在各自范围内线性关系良好，相关系数(r²)>0.995;方法检出限为马尿酸(HA)0.9 mg/L,其余目标化合物0.02～4μg/L,定量限为HA 3 mg/L,其余目标化合物0.05～12μg/L;在实际尿液中低、中、高3个水平的加标回收率为84%～123%,日内精密度为1.8%～8.6%,日间精密度为1.9%～21.4%。应用该方法测定吸烟和非吸烟人群尿液样品各16份，吸烟人群中7种目标化合物检出率均为100%;非吸烟人群中反-反式黏糠酸(MU)、苄基巯基尿酸(BMA)、HA和2-甲基马尿酸(2MHA)的检出率为100%,(S)-苯巯基...     

固相萃取-高效液相色谱-串联质谱法同时测定尿液中的4种巯基尿酸

建立了固相萃取-高效液相色谱-串联质谱(HPLC-MS/MS)同时检测人体尿液中N-乙酰基-S-(3,4-二羟基丁基)-L-半胱氨酸(DHBMA)、N-乙酰基-S-(3-羟基丙基)半胱氨酸(3-HPMA)、N-乙酰基-S-(2-氰乙基)-L-2-氨基-3-巯基羧酸(CEMA)和苯巯基尿酸(SPMA)的检测方法。冰冻的人体24 h尿液在室温下解冻,混合均匀后离心过滤,经C18固相萃取小柱净化富集后在多反应监测模式下采用HPLC-MS/MS进行定量分析。在3个添加水平下,尿液中DHBMA、3-HPMA、CEMA和SPMA的加标回收率分别为105.6%～124.4%、102.7%～106.5%、103.2%～103.9%和101.7%～104.3%,相对标准偏差为2.6%～7.7%。以不低于3倍的信噪比估算DHBMA、3-HPMA、CEMA和SPMA的检出限分别为0.062、0.031、0.020和0.003 μg/L。应用该方法检测了37例吸烟和非吸烟者的24 h尿液样本,结果发现吸烟者尿液中3-HPMA、SPMA和CEMA的平均含量比非吸烟者高3到6倍。     

大鼠尿液与粪便中氟噻草胺的UPLC-MS/MS法测定

建立了一种测定大鼠尿液和粪便中氟噻草胺含量的超高效液相色谱-串联质谱(UPLC-MS/MS)分析方法。粪便与尿液样品采用乙腈提取;液相色谱分离采用Phenomenex反向C18色谱柱(50 mm×4. 6 mm,5μm),以0. 1%甲酸水和乙腈为流动相,流速0. 6 m L/min;质谱检测采用电喷雾离子源,正离子模式和多反应监测(MRM)方式进行扫描。结果表明:氟噻草胺在尿液(0. 10～10. 0 mg/L)和粪便(0. 25～50. 0 mg/L)中线性关系良好,相关系数r 0. 99,尿液和粪便中氟噻草胺的定量下限分别为0. 10 mg/L和0. 25 mg/L;质控样品的日内与日间相对标准偏差不大于9. 9%。样品稳定性为93. 7%～108%,尿中平均提取回收率为97. 0%～98. 8%,基质效应为98. 8%～107%,均符合生物分析方法验证的要求。考察了大鼠单次灌胃给予氟噻草胺400 mg/kg后的排泄动力学,144 h内尿液与粪便的总累积排泄率为12. 62%,其中尿中的累积排泄率为1. 12%,粪便中的累积排泄率为10. 13%,表明氟噻草胺主要经粪便排泄。该法灵敏、专属、准确,可用于大鼠尿液、粪便中氟噻草胺浓度的测定。     

加压毛细管电色谱法测定肥胖大鼠尿液中内源性代谢物

利用氯甲酸乙酯作为衍生化试剂,建立了测定尿样中内源性代谢物的加压毛细管电色谱方法。采用毛细管色谱柱EP-150-30/50-5-C18,以0.01%TFA水溶液(A)与0.01%TFA的95%乙腈水溶液(B)组成流动相,加压13MPa;工作电压为2kV;流速0.08mL/min;检测波长214nm;室温;柱上检测;进样体积5μL,同时测定了正常大鼠尿液与肥胖大鼠尿液中几种代谢物的含量。在最佳条件下,6种内源性代谢物在1.2～500mg/L范围内线性良好,相关系数为0.9988～0.9999;日间和日内精密度小于5%;平均加样回收率在95.9%～103.2%之间。本方法用于大鼠尿液中内源性代谢物含量的测定,简单、灵敏、准确。     

固相萃取-气相色谱-质谱法检测尿液中乙基葡萄糖醛酸苷

建立了固相萃取(SPE)-气相色谱-质谱(GC-MS)检测尿液样本中乙基葡萄糖醛酸苷(EtG)的方法.1 mL尿液样本经100μL 3 mol/L盐酸去蛋白后,通过SPE法提取上清液中的目标物质及内标,提取物经衍生化后,采用GC-MS检测,选择离子模式(SIM)扫描,内标法定量分析.该方法在0.1～3.2 mg/L范围...     

高效液相色谱-紫外检测法测定人体尿液中的蝶呤-6-羧酸

建立了人体尿液中蝶呤-6-羧酸的高效液相色谱-紫外分析新方法. 运用Lichrospher C18柱(250×4.6 mm,5 μm),甲醇-水(70∶30,V/V)为流动相,流速为0.4 mL/min,可较好地将尿液中蝶呤-6-羧酸与其它共存干扰物质分离.在355 nm检测波长下,蝶呤-6-羧酸在0.19～4.8 μg/mL范围内与色谱峰面积呈良好线性关系,相关系数为0.9999,方法检出限为0.015 μg/mL.尿液经0.45 μm滤膜过滤后,可直接进样分析,方法简便,应用于癌症病人和健康人尿样中蝶呤-6-羧酸测定,结果较好.方法的加标回收率为94.6%～100.2%,相对标准偏差为0.81%～ 5.07% .     

UPLC-MS/MS法测定高尿酸血症大鼠血清及尿液中的尿酸和肌酐

建立了一种测定血清和尿液中尿酸和肌酐含量的超高效液相色谱-串联质谱联用（UPLC-MS/MS）方法. 样品经自动进样器引入液相色谱通过预柱富集和去除杂质后,直接引入质谱中进行分析. 采用正离子电喷雾电离模式下的多反应监控模式对肌酐进行定量分析,纯溶剂标准曲线的肌酐线性范围为0.03~400 μmol/L;基质标准曲线的肌酐线性范围为0.2~400 μmol/L;它们的最低定量限分别为0.03和0.2 μmol/L. 采用负离子电喷雾电离模式下的多反应监控模式对尿酸进行定量分析,纯溶剂标准曲线的尿酸线性范围为0.1~350 μmol/L;基质标准曲线的尿酸线性范围为0.5~300 μmol/L;它们的最低定量限分别为0.1和0.5 μmol/L. 该方法的提取回收率在91.8%~103.7%之间,日内和日间RSD分别小于5.9%和6.8%,满足生物分析的要求. 利用该方法进行抗痛风中药筛选及其作用机制研究,结果表明,与阳性对照药物别嘌呤醇和苯溴马隆相比,中药二妙丸、黄柏和苍术均能在一定程度上降低血尿酸水平,并可显著逆转肾功能损伤,对肾功能具有一定的保护作用.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

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.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

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.