共振瑞利散射法测定多柔比星脂质体中游离多柔比星的含量

目的:建立共振瑞利散射法(RRS)测定多柔比星(DOX)脂质体中游离 DOX 含量。方法:在 pH 2.6的 Britton-Robinson(BR)缓冲液中,刚果红(CR)与 DOX 通过分子间作用力形成离子缔合物,在λ_(ex)=λ_(em)=380 nm 波长时能使 RRS 信号显著增强。结果:RRS 法在1～12 μg·mL~(-1)范围内呈线性关系,检出限为0.05~(-1)g·mL~(-1)。对6个不同批号的 DOX 脂质体混悬液中游离 DOX 的含量测定,结果与紫外可见分光光度法相符,RSD(n=6)为1.9%～3.2%,平均回收率为94.3%。结论:此方法灵敏度较高,可以用于测定 DOX 脂质体中游离 DOX 的含量。     

HPLC荧光检测法测定人血浆中的罗格列酮钠

目的 采用HPLC荧光检测法测定人血浆中的罗格列酮钠.方法 用Agilent C_(18)色谱柱(150mm×4.6 mm,5 μm),以乙腈-pH3磷酸盐缓冲液(35:65)为流动相,流速1.0 mL·min~(-1),进样量20μL,血浆样品经乙醚提取后进样,荧光检测器检测波长λ_(ex)=250 nm,λ_(em)=370 nm.结果 罗格列酮钠的线性范围为10～1000 ng·mL~(-1)(r=0.9999),最低定量限为10 ng·mL~(-1)(S/N>3),日内RSD<4%(n=5),日间RSD<16%(n=5),萃取回收率>94.81%.结论 所建方法适用于临床上罗格列酮钠片的血药浓度监测及药动学的研究.     

荧光分光光度法测定何首乌及人参首乌胶囊中总蒽醌的含量

目的:建立测定何首乌及人参首乌胶囊中总蒽醌含量的方法。方法:荧光分光光度法。以最佳 pH 条件的无水乙醇为溶剂,在λ_(EX)=440nm、λ_(EM)=515nm 处测定总蒽醌含量。结果:在0.03～0.15μg·mL~(-1)范围内,大黄素浓度和荧光强度有良好的线性关系,回归方程为 F=194.36C 2.9642,r=0.9996。平均回收率何首乌为98.1%,RSD 为1.9%;人参首乌胶囊为98.6%,RSD 为2.0%。测得总蒽醌含量何首乌中为0.522 mg·g~(-1),人参首乌胶囊中为0.443mg·g~(-1)。结论:本法简便快捷,准确灵敏,重复性好,可用于何首乌及人参首乌胶囊的质量控制。     

荧光法测定小鼠体内各组织中环丙沙星的浓度

目的:测定小鼠体内各组织中环丙沙星的浓度。方法:采用三氯化铝络合环丙沙星-荧光分光光度法。结果:在λ_(ex)=330 nm,λ_(em)=440 nm处,络合物的荧光值不受各组织的影响,且比环丙沙星自身的荧光值增加了20倍,线性范围为50～1000ng·mL~(-1)。结论:此方法准确、快速,适用于环丙沙星的体内研究。     

抗凝药物华法林的荧光光谱测定方法研究

目的:基于华法林钠的荧光光谱特性,以水-乙醇混合溶剂为介质,研究建立了一种测定华法林钠的荧光光谱分析方法。方法:水-乙醇的最适宜配比为3:7,该体系的最大激发波长(λ_(ex))和发射波长(λ_(em))分别为308 nm 和386 nm,测定系列标准溶液在测定波长下的荧光强度,并计算样品中华法林钠的含量。结果:在所选的最佳试验条件下,华法林钠浓度在0.3～7.1μg·mL~(-1)范围内与荧光强度具有良好的线性关系,检出限为0.1μg·mL~(-1),回收率为96.7%～104.9%。结论:本方法可应用于药物华法林钠含量的测定。     

高效液相色谱荧光检测法测定人血浆中替米沙坦浓度及其应用

目的:建立高效液相色谱荧光检测人血浆中替米沙坦浓度的方法,并用于研究替米沙坦片的人体药代动力学。方法:采用固相萃取方法提取血浆中的替米沙坦,色谱柱为 Diamonsil C_(18)柱(5μm,4.6mm×150mm),以乙腈-磷酸二氢钾缓冲液(61∶39,磷酸调 pH=3.74)为流动相,流速1.0mL·min~(-1),坎地沙坦为内标,荧光检测波长λ_(Ex)=305nm,λ_(Em)=365nm。结果:本法测定替米沙坦的线性范围为0.5-144ng·mL~(-1),r=0.9998,绝对回收率在79.62%-85.69%(n=5),相对回收率在101.9%-109.0%(n=5),日内和日间 RSD 分别为4.23%-9.80%和4.03%-9.95%(n:5)。结论:本法灵敏、准确,操作简捷,适用于替米沙坦的血药浓度测定及药代动力学研究。     

荧光猝灭法测定盐酸胺碘酮含量

目的:建立荧光猝灭法测定盐酸胺碘酮片剂含量的新方法。方法:试验多种荧光试剂加入系列浓度的胺碘酮溶液,测定其荧光光谱的变化。结果:选用芘丁酸(PBA)为荧光试剂,浓度为2.0mg·L~(-1),λ_(ex)/λ_(em)=349nm/376.3nm,在2.0～20mg·L~(-1)胺碘酮浓度范围与荧光猝灭值(F_0/F)成良好的线性关系(r=0.9962),据此提出测定片剂中胺碘酮含量的荧光猝灭法。结论:荧光猝灭法简便灵敏、选择性高,可用于药片中盐酸胺碘酮含量的测定。     

环丙沙星荧光特性的研究

目的:建立荧光测定环丙沙星含量的方法,对几种金属离子(Fe~(3+),Cu~(2+),Zn~(2+))与环丙沙星的络合反应及其对荧光特性的影响作初步的研究。方法:用日立荧光分光光度计测定,测量波长λ_(ex)=277 nm,λ_(em)=450nm。测定时的最佳pH为2.2。结果:环丙沙星浓度在0.1～0.8mg·L~(-1)范围内与荧光强度呈线性关系,相关系数为0.9999,检测限为4.5×10~(-3) mg·L~(-1)。结论:该法方便、快速,可用于直接测定环丙沙星含量,或用于微量分析。     

高效液相色谱-荧光检测法测定红景天苷的含量

目的:建立高效液相色谱-荧光检测法测定红景天苷的含量。方法:色谱柱为 Eclipse XDB-C_8柱(4.6 mm × 150 mm,5μm),流动相为水-甲醇(85:15),流速为1.0 mL·min~(-1),柱温为25℃,荧光检测波长λ_(EX)=220 nm,λ_(EM)=315 nm。结果:该方法的线性范围为1.00～500 ng(r=0.999 9)。平均加样回收率为 99.2％,RSD为 1.4％(n=5)。最低检测限为1.5 pg。结论:本方法快速,简单,灵敏度极高。     

HPLC—MS／ESI法测定人血浆中文拉法新及其代谢产物氧去甲基文拉法新对映体血药浓度

目的:建立反相高效液相色谱-质谱法同时测定人血浆巾文拉法新(VEN)及其主要代谢产物氧去甲基文拉法新(ODV)对映体的浓度。方法:使用万古霉素手性柱(CHRIOBIOTIC V~(TM))(250 mm×4.6 mm,5 μm),以甲醇-醋酸铵缓冲液(30 mmol·L~(-1))(15:85,pH 6.0)为流动相对两化合物进行手性拆分,流速设为1.0 mL·min~(-1),柱后分流比为3:1。采用质谱电喷雾电离正源(ESI~ )将样品离子化,选择性离子监测(SIM)准分子离子峰。结果:在所建立的色谱条件下,VEN 与 ODV得到很好的手性分离。S-( )与 R-(-)-VEN 在5.0～400 ng·mL~(-1)S-( )与 R-(-)-ODV 在4.0～300 ng·mL~(-1)范围内线性关系良好,相关系数均大于0.9991;萃取回收率均大于76%;方法回收率均大于92%;最低检测浓度:S-( )与R-(-)-VEN 为1.0 ng·mL~(-1),S-( )与 R-(-)-ODV 1.5ng·mL~(-1);日内及日间 RSD 均小于9%。结论:本方法简单、快速、灵敏、准确,可用于 VEN 人体内立体选择性代谢的研究。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

The pathogenesis of,and pharmacological treatment for,Canavan disease

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Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

甘草甜素脂质体和甘草甜素的药动学比较

目的:比较健康志愿者口服甘草甜素脂质体(Glycyrrhizin liposome,GL-L)和甘草甜素药片(Glycyrrhizin,GL)后的药动学.方法:用高效液相色谱检测血浆甘草次酸(Glycyrrhetinic acid,GA)的浓度,流动相为甲醇-水-醋酸-三乙胺(87:12.15:0.3:0.55),流速为1.0 mL·min-1,用乙腈提取,在254 nm下检测.用上述HPLC法测定8例健康志愿者口服GL-L和GL后的药动学.结果:血浆GA的出峰时间大约为12 min,检测限为0.062 5μg·mL-1.口服两种制剂后,血浆中未检测到GL,仅检测到GA,口服GL-L后血中GA的浓度-时间曲线下面积(AUC)、血药峰值(Cmax)较口服GL高.结论:口服GL很少被吸收,而口服GL-L后可促进GL转变为GA和GA的吸收.     

Spectral data analyses and structure elucidation of metoprolol tartrate

The infrared spectrum, ultraviolet spectrum, mass spectra, and nuclear magnetic resonance spectra of metoprolol tartrate, an antiarrhythmic medicine, were reported and interpreted comprehensively. The vibrations of functional groups in infrared spectrum, electron transitions in ultraviolet spectrum, and main characteristic fragmentations in mass spectra of metoprolol tartrate were discussed. All the (1) H and (13) C NMR chemical shifts were assigned by means of distoritionless enhancement by polarization transfer-135 and -90, (1) H-(1) H correlation spectroscopy, and (13) C-(1) H correlation spectroscopy via short- and long-range coupling.     

Identification and Assessment of Tumor-Promoting and Cocarcinogenic Agents: State-of-the-Art in Vitro Methods

Abstract

Chemical-analytical studies during the past 4 years led to several new observations on the formation of tobacco-specificN-nitrosamines (TSNA) and their occurrence in smokeless tobacco, mainstream smoke (MS), and sidestream smoke (SS) of American and foreign cigarettes. When snuff was extracted by means of supercritical fluid extraction with carbon dioxide containing 10% methanol, analysis of this material confirmed that the extraction with organic solvents had been partially incomplete.

Epidemiological studies in the northern Sudan showed a high risk for oral cancer for users of toombak, a home-made oral snuff. Toombak contains 100-fold higher levels of TSNA than commercial snuff in the U.S. and Sweden. The TSNA content in the saliva of toombak dippers is at least ten times higher than that reported in the saliva of dippers of commercial snuff. Biomarker studies have shown corresponding high levels of hemoglobin adducts with metabolites of NNN and NNK as well as for urinary metabolites of NNK. These data supported the epidemiological findings.

The analyses of MS of U.S. and foreign cigarettes smoked under FTC conditions revealed comparable data for the smoke of nonfilter cigarettes and filter cigarettes except in the case of low- and ultralow-yield cigarettes, which showed reduced TSNA yields. The MS of cigarettes made from Burley or dark tobacco is exceptionally high in TSNA, primarily because of the high nitrate content of those tobacco types. Taking puffs of larger volume and drawing puffs more frequently, practices observed among most smokers of cigarettes with low nicotine yield, results in high TSNA values in the MS. The formation of the lung carcinogen NNK is favored during the smoldering of cigarettes, between puffs, when SS is generated. Consequently, in most samples from indoor air polluted with environmental tobacco smoke (ETS), the highest concentration of an individual TSNA is that of NNK. When nonsmokers had remained for up to 2 h in a test laboratory with high ETS pollution, they excreted measurable amounts of NNK metabolites in the urine, indicative of the uptake of TSNA.     

高效毛细管电泳法测定磺胺类药物的离解常数及其制剂的含量

目的:采用毛细管电泳法测定磺胺甲唑(sMZ)、磺胺嘧啶(SD)和甲氧苄啶(TMP)的离解常数及其在制剂中的含量。方法:采用未涂层的弹性石英毛细管柱(60.2 cm×75 μm,有效长度50 cm),柱温25 ℃,正极压力进样,检测波长214 nm。将3种化合物的有效电泳淌度与 pH 进行非线性拟合,测定其离解常数;最佳的分离条件为:50 mmol·L~(-1)磷酸二氢钠(pH 6.0)缓冲液,分离电压27.5 kV,在此条件下测定其在制剂中的含量。结果:SMZ、SD、TMP 的离解常数分别为5.69,6.36,6.68;在0.1～1000μg·mL~(-1)的浓度范围内线性关系良好(相关系数:0.9992～0.9999),回收率为95.6%～105.0%。结论:该方法简便、快速、准确,可用于测定3种磺胺类药物的解离常数及其在制剂中的含量。     

依那普利抗异丙肾上腺素诱导的心肌纤维化作用及机制

目的观察依那普利(enalapril,Ena)抗异丙肾上腺素(Isoprenaline,Iso)诱导的心肌纤维化作用并探讨其作用机制。方法异丙肾上腺素皮下注射致心肌纤维化模型,经Ena低、中、高(2.5、5.0、10.0 mg.kg-1)3个剂量组和阳性对照药卡托普利(100.0 mg.kg-1)治疗后观察其对心肌组织胶原变化、心室重量(HW/BW)和心室重量指数(LVI)、羟脯氨酸含量及免疫组化和Western blot检测TGF-β1表达的影响。结果Ena不同剂量组均能够降低心肌组织胶原含量(P<0.05或P<0.01),降低HW/BW和LVI(P<0.05或P<0.01),降低羟脯氨酸含量(P<0.05或P<0.01),减少TGF-β1在心肌组织中的表达(P<0.05或P<0.01),减轻心肌纤维化。结论Ena通过抑制TGF-β1表达抗Iso诱导的心肌纤维化。