芸香甙的药代动力学研究

目的研究芸香甙在兔体内的药代动力学。方法家兔一次静注芸香甙５ｍｇ·ｋｇ－１后，利用荧光分光光度法测定不同时间的血药浓度。应用３Ｐ８７药动学软件程序对数据进行计算机处理。结果芸香甙的药时（Ｃ－Ｔ）方程为：Ｃ＝８５．９７８９ｅ－０．９０４４Ｔ＋３４．５１０５ｅ－０．０５８７Ｔ＋４．３８３８ｅ－０．００４６Ｔ。芸香甙的主要药代动力学参数如下：Ｔ１／２ａ：（０．７６０９±０．１０６６）ｍｉｎ，Ｔ１／２ｂ：（１２．５６６７±３．７１３９）ｍｉｎ，Ｔ１／２ｃ：（１６２．５６５１±５０．６０３５）ｍｉｎ，Ｋ１２：（０．５１２３±０．１３１６）ｍｉｎ－１，Ｋ２１：（０．３２９８±０．０７３７）ｍｉｎ－１，Ｋ１３：（０．０７３９±０．０１８２）ｍｉｎ－１，Ｋ３１：（０．０１００±０．００３７）ｍｉｎ－１，Ｋ１０：（０．０７７４±０．０１６０）ｍｉｎ－１，Ｖｃ：（０．０４０４±０．００４４）Ｌ·ｋｇ－１，ＡＵＣ：（１６７９．７５８３±４８０．６０４５）ｍｇ·Ｌ－１·ｍｉｎ－１，ＣＬ（ｓ）：（０．００３１±０．０００８）Ｌ·ｋｇ－１·ｍｉｎ－１。结论芸香甙在兔体内的Ｃ－Ｔ变化符合三室开放模型；芸香甙在体内的分布、消除迅速。     

cGMP介导以注入L—精氨酸诱导的大鼠血管加压素释放效应

目的：探讨ｃＧＭＰ是否介导Ｌ－精氨酸（一氧化氮合酶物）引起的血管加压素（ＡＶＰ）释放增多效应。方法：用放射免疫法测定大鼠血浆中ＡＶＰ水平。结果：侧脑室分别注射Ｌ－精氨酸和８－溴－ｃＧＭＰ（一种可透过膜的ｃＧＭＰ衍生物）能刺激血浆ＡＶＰ水平增加［分别从（３．２±０．５）升至（５．８±１．４）ｎｇ·Ｌ＾－１，从（２．６±０．３）升至６６．６±０．４）ｎｇ·Ｌ＾－１，Ｐ〈０．０１］，同时注射Ｌ－精氨酸和     

糖尿病大鼠血中内源性一氧化氮合酶抑制物增高

目的：测定糖尿病大鼠血中内源性ＮＯ合酶抑制物二甲基精氨酸（ＤＭＡ）的含量，方法：在链佐星诱发的糖尿病大鼠测定血清ＤＭＡ的含量和乙酰胆碱（ＡＣｈ）诱导血管内皮依赖性舒张，结果：与对照组相比，糖尿病大鼠ＤＭＡ血清浓度显增加（５．４±１．０ｖｓ０．７±０．３μｍｏｌ．Ｌ＾－１，Ｐ〈０．０１）；丙二醛含量也高于对照组（２．５±０．３ｖｓ２１．５±０．１μｍｏｌ．Ｌ＾－１，Ｐ〈０．０１）；糖尿病大鼠ＡＣｈ     

组氨酸对大鼠血栓性脑缺血时心肌线粒体及血小板聚集的影响

目的：研究组氨酸对脑血栓形成的影响及可能机制。方法：采用光化学诱导“脑－心卒中”模型并给组氨酸（ｉｖ ５ｍｇ·ｋｇ＾－１）治疗。结果：脑血栓形成后４和２４ｈ全血血小板聚集的峰值为（５．１±０．５）Ω和（４．３±０．５）Ω。心肌线粒体体积（Ｖ）、体密度（Ｖｖ）、面密度（Ｎｍ）及外膜表面（Ｓｖ１）增加（８．２±５．５，０．５９±０．１６，０．１１±０．０３和２．２±０．０５，Ｐ〈０．０１），但数密度（     

利巴韦林及聚肌胞分别治疗流行性腮腺炎和水痘

流行性腮腺炎７８例（男性３３例，女性４５例；年龄５．７±ｓ２．５ａ）的及水痘２８例（男性１２例，女性１６例；年龄６．３±２．２ａ），用利巴韦林５－７．５ｍｇ／ｋｇ，ｉｍ，ｂｉｄ，治疗３－６ｄ。结果：腮腺消肿时间４．３±１．９ｄ，水痘结痂时间为３．６±１．６。另有流行性腮腺炎３５例（男性１６，女性１９例；年龄５．２±２．３ａ），的水痘２５例（男性１１例，女性１４例；年龄５．７±２．３ａ），用聚肌胞注射液１－２ｍｇ，ｉｍ，ｑｏｄ，成治疗３－６ｄ。结果：腮腺消肿时间为６±３ｄ，水痘结痂时间为５．２±２．０ｄ。利巴韦林组显著优于聚肌胞组（Ｐ＜０．０１及０．０５）。     

头孢哌酮与氧氟沙星治疗伤寒的比较

用头孢哌酮治疗伤寒２５例（男性１５例，女性１０例；年龄２５±ｓ１０ａ），４ｇ／ｄ，分２次ｉｖ。热退后继续用药３－５ｄ。用氧氟沙星治疗２７例（男性１３例，女性１４例；年龄２６±１０ａ），０．６ｇ／ｄ，分３次ｐｏ。热退后继续用７ｄ。结果：２组服药后体温开始下降时间分别为１．５±０．６和２．３±１．２ｄ（Ｐ＜０．０１），体温降至正常时间分别为３．６±１．２ｄ和５．０±１．６ｄ（Ｐ＜０．０１），说明头孢哌     

气相色谱法测定人参中六氯苯残留量

选用气相色谱法，以０．３％ＯＶ－１７＋３％ＯＦ１为固定相，外标法测定了人参中甲乙丙丁体六氯苯的残留量，测得回收率分别为（９４．１±５．８３）％，（９７．０±３．５６）％，（９４．４±３．３５）％和（９３．６±５．５３％）（ｎ＝５）．     

高效液相色谱法测定人血清中西替利嗪及其药动力学

目的：建立高效液相色谱法测定人血清中西替利嗪。方法：用ＨＰＬＣ法检测８名健康自愿者血中西替利嗪浓度,经３Ｐ８７程序拟合,计算药动学参数。结果：西替利嗪药动学参数Ｔ１／２ａ,Ｔ１／２β,Ｔｍａｘ,Ｃｍａｘ,Ｖ／Ｆ和ＡＵＣ分别为（１．６±０．８）ｈ,（７．２±１．１）ｈ,（１．３±０．４）ｈ,（３７４．７±６１．８）ｎｇ．ｍｌ＾－１,（３９．１±８．８）Ｌ和（３１８８．４±２４６．１）ｎｇ．ｈ．ｍｌ＾     

复方磺胺甲恶唑分散片在正常人体内的药代动力学及相对生物利用度

本文采用ＨＰＬＣ法同时测定血浆中复方磺胺甲恶唑分散片中ＳＭＺ和ＴＭＰ的浓度,采用ＨｙｐｅｓｉｌＯＤＳ柱,流动相为乙腈：醋酸钠（ｐＨ６．４０．１ｍｏｌ／Ｌ）＝２２：７８（Ｖ／Ｖ）,检测波长２３０ｎｍ,流速为１．００ｍｌ／ｍｉｎ。１０名志愿受试者自身交叉口服Ｃｏ－ＳＭＺ片和Ｃｏ－ＳＭＺ分散片８００ｍｇ。结果显示ＳＭＺ和ＴＭＰ的Ｃｍａｘ分别为４６．６９±７．ｄ６６ｕｇ／ｍｌ,４４．６１±６．３７ｕｇ／ｍｌ和１．８２±０．４９ｕｇ／ｍｌ,１．６３±０．４３ｕｇ／ｍｌ;Ｔｍａｘ为３．４１±１．５９ｈ,３．４±０．８４ｈ和１．４８±０．８３ｈ,１．５０±０．８１ｈ：ＡＵＣ为９６１±１２９．３７ｕｇ．ｈ／ｍｌ,７６１．７９±１４５．６ｕｇ．ｈ／ｍｌ和２６．９１±３．８９ｕｇ．ｈ／ｍｌ,２６．９６±４．７１ｕｇ．ｈ／ｍｌ,分散     

大鼠后肢热诱导的缓激肽和P物质的释放

用放射免疫法测定缓激肽（ＢＫ）和Ｐ物质（ＳＰ）含量。发现正常大鼠（Ｂ／Ｎ－Ｋｉ）左后肢用４７℃，热水刺激２０ｍｉｎ，后肢足跖皮下灌流液中ＢＫ和ＳＰ含量分别为４３±３４和１１．１±９．７ｆｍｏｌ·ｍｉｎ＾－１，比热刺激前显增加，但在血浆激肽原缺乏大鼠（Ｂ／Ｎ－Ｋａ），ＢＫ和ＳＰ含量分别为１．３±１．０和５．５±３．５ｆｍｏｌ·ｍｉｎ＾－１，明显低于Ｂ／Ｎ－Ｋｉ大鼠。Ｂ／Ｎ－Ｋａ大鼠的Ｅｖａｎｓ蓝漏     

Improved LC of minocycline drug substance

An isocratic liquid chromatographic method is described for the separation of minocycline and its impurities. This method uses XTerra RP-18, 5 microm (25 cm x 4.6 mm I.D.), a silica-based stationary phase with reduced silanol activity. A mobile phase composed of acetonitrile-0.2 M tetrabutylammonium hydrogen sulphate pH 6.5-0.2 M ethylenediaminetetraacetic acid pH 6.5-water (20:20:20:40; v/v/v/v) was used at a flow rate of 1 ml/min. The column temperature was set at 35 degrees C. UV detection was performed at 280 nm. Optimisation of the separation method and a robustness study were performed by means of a central composite experimental design. The method allows to separate minocycline from known impurities. Some unidentified impurities are also separated. The total time of analysis is less than 20 min.     

HPLC法测定盐酸米诺环素缓释微丸胶囊中的米诺环素和有关物质

目的建立反相HPLC法测定盐酸米诺环素缓释微丸胶囊中米诺环素的量和有关物质。方法 Diamonsil C18柱(200mm×4.6mm,5μm),流动相为醋酸铵缓冲溶液(pH6.0)-乙腈-甲醇(80:15:5),检测波长为280nm,体积流量为1.0mL/min,柱温为25℃,进样量为20μL。结果米诺环素在0.05～1mg/mL线性关系良好(r=0.9997),方法精密度RSD为0.6%,平均回收率为99.46%,RSD为0.8%,各杂质峰与主峰分离良好。结论该方法简便,专属性强,准确可靠,可用于测定盐酸米诺环素缓释微丸胶囊中的米诺环素及有关物质。     

Minocycline attenuates ischemia-induced ventricular arrhythmias in rats

Minocycline has been shown to protect against myocardial ischemia–reperfusion injury. This study investigated the effects of minocycline on ischemia-induced ventricular arrhythmias in rats. Anesthetized male rats were once treated with minocycline (45 mg/kg, i.p.) 1 h before ischemia in the absence and/or presence of 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002, 0.3 mg/kg, i.v., a PI3K inhibitor) and 5-hydroxydecanoic acid [5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium (K_ATP) channels] which were once injected 10 min before ischemia and then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed. L-type Ca²⁺ current was measured by the patch-clamp technique. During the 30-minute ischemia, minocycline significantly reduced the incidence of ventricular fibrillation (VF) (P < 0.05). The duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by minocycline compared to those in myocardial ischemia group (P < 0.05 for all). Administration of LY294002 or 5-HD abolished the protective effects of minocycline on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (P < 0.05 for all). In addition, minocycline inhibited L-type Ca²⁺ currents of normal myocardial cell membrane in a dose-dependent manner. This study suggested that minocycline could attenuate ischemia-induced ventricular arrhythmias in rats in which PI3K/Akt signaling pathway, mitochondrial K_ATP channels and L-type Ca²⁺ channels may be involved_.     

反相高效液相色谱法测定人血浆中二甲胺四环素浓度

目的:建立以反相高效液相色谱法测定人血浆中二甲胺四环素浓度的方法。方法:色谱柱为C18,流动相为乙腈-水-三氟乙酸(15∶85∶0.1),内标为土霉素,检测波长为350nm,血样在pH=6.5缓冲液条件下用乙酸乙酯提取,以二甲胺四环素与内标的峰面积比进行定量。结果:二甲胺四环素检测浓度线性范围为0.05～8μg/ml(r=0.9999),最低检测浓度为0.02μg/ml,平均回收率为101.89%,日内、日间相对标准差均小于5%。结论:本方法简便、快速、灵敏,可用于二甲胺四环素药动学研究。     

Analysis of tetracycline antibiotics and their common impurities by high-performance liquid chromatography using a polymeric column

The chromatographic separation of tetracycline, oxytetracycline, 6-demethyl-chlortetracycline, methacycline and minocycline, and the common impurities of tetracycline, oxytetracycline and chlortetracycline has been optimised on a Hamilton PRP-1 column using citrate-phosphate buffer with propan-2-ol and tetrahydrofuran as organic modifiers. Column efficiency was approximately doubled by the inclusion of 1% v/v dichloromethane in the mobile phase.     

Assay and purity control of minocycline by thin-layer chromatography using UV and fluorescence densitometry — a comparison with liquid chromatography

A thin-layer chromatography (TLC) method using UV and fluoresecence densitometry is described for the assay and purity control of minocycline (MC). With a mobile phase dichloromethane-methanol-water (57:35:8, v/v/v) and a silica gel thin-layer, previously sprayed with 10% m/v sodium edetate adjusted to pH 9.0, 4-epiminocycline and 7-didemethylminocycline were well separated from MC and from each other, 7-monodemethylminocycline and 6-deoxy-6-demethyltetracycline (6-DODMTC) were not separated from each other and were only partially separated from minocycline. 6-DODMTC was selectively determined by fluorescence densitometry, while quantification of other impurities and the assay of MC were performed by UV densitometry. Results obtained with qualitative TLC were compared with those obtained by a liquid chromatography (LC) method using a poly(styrene-divinylbenzene) copolymer stationary phase. The correlation coefficient for TLC and LC results was >0.999. For TLC the relative standard deviation for the assay of MC at 1.25 mg ml⁻¹ was < 3.0% (n = 4), while for LC it was < 1.0% (n = 4).     

高效液相色谱法测定人血清中二甲胺四环素的浓度及其药代动力学研究

建立了反相高效液相色谱法测定二甲胺四环素的血药浓度。柱C18；以己腈-0．lmol／L枸橼酸溶液（15：85）为流动相，在353nm处测定。以土霉素为内标，血样在pH6．5条件下用乙酸乙酯提取；用二甲胺四环素与内标的峰高比进行定量。线性范围0．5～7μg／ml（Y=0．9994），最低检测限50ng／ml；平均回收率92．84％；日间RSD＜5％。应用本法研究了8名健康志愿者单次口服200mg盐酸二甲胺四环素胶囊后的药代动力学，符合二室开放模型，于2．4h达血峰浓度3．42±0．63μg／ml；AUC为77．12±16．89mg．h／L；t1/2为20．61±3．22h。     

高效液相色谱-电化学检测器法测定人肝微粒体中雌二醇的代谢产物(英文)

目的:建立雌二醇在人肝微粒体中代谢产物的测定方法,研究低浓度雌二醇在人肝微粒体中的代谢机制。方法:有机溶剂提取、蒸发、重溶的方法处理样品,高效液相色谱法分离组分,电化学检测器测定含量。结果:流动相为醋酸缓冲液-乙腈(50:50,v/v,pH4.5,电压为 0.7V vs Ag/AgCl时,在C18柱上分离较好。最低检测量为100pg。结论:本法可用于测定底物浓度在1-100μmol/L时,人肝微粒体中的代谢产物。     

Development and Validation of RP-HPLC Method for Simultaneous Estimation of Atorvastatin Calcium and Fenofibrate in Tablet Dosage Forms

A reverse phase high performance liquid chromatographic method was developed for the simultaneous estimation of atorvastatin calcium and fenofibrate in tablet formulation. The separation was achieved by Luna C18 column and methanol:acetate buffer pH 3.7 (82:18 v/v) as mobile phase, at a flow rate of 1.5 ml/min. Detection was carried out at 248 nm. Retention time of atorvastatin calcium and fenofibrate was found to be 3.02+0.1 and 9.05+0.2 min, respectively. The method has been validated for linearity, accuracy and precision. Linearity for atorvastatin calcium and Fenofibrate were in the range of 1-5 μg/ml and 16-80 μg/ml, respectively. The mean recoveries obtained for Atorvastatin calcium and fenofibrate were 101.76% and 100.06%, respectively. Developed method was found to be accurate, precise, selective and rapid for simultaneous estimation of atorvastatin calcium and fenofibrate in tablets.     

超快速液相色谱法测定新型“K2”香料中JWH-018的含量

目的:建立测定新型"K2"香料中JWH-018含量的超快速液相色谱法。方法:采用Shim-pack XR-ODSⅡ色谱柱(2.0 mm×75 mm,2.2μm);流动相:乙腈(含0.1%甲酸)-水(含0.1%甲酸)(80:20,v/v),流速:0.25 mL·min-1;检测波长280 nm,柱温:35℃,进样量:2μL,外标法定量测定JWH-018的含量。结果:JWH-018的浓度在1-1000μg·mL-1范围内线性良好(A=8419.8C+13932,r=1.0000);最低检测限为90 ng·mL-1(S/N=3);低、中、高3种浓度的加样回收率(n=3)分别为101.0%(RSD=0.28%),101.0%(RSD=0.63%),101.7%(RSD=0.03%)。结论:本法操作简便、灵敏、准确,重复性好,适用于"K2"香料中JWH-018含量的测定。