HPLC法同时测定人血浆中顺铂和环磷酰胺的浓度

目的:建立同时测定人血浆中环磷酰胺(CTX)和顺铂(DDP)浓度的方法。方法:采用双波长高效液相色谱法,色谱柱为Hypersil-ODS2,流动相为甲醇-水(80∶20),检测波长为254 nm(DDP)、195 nm(CTX),流速为1 mL·min-1。结果:CTX、DDP保留时间分别为5.15、9.26 min,血药浓度分别在0.5～10μg·mL-1(r=0.999 9)、0.1～2.0μg·mL-1(r=0.999 8)范围内线性关系良好,检测限各为0.1、0.02μg·mL-1(S/N≥3);方法回收率分别为96.0%～98.4%、97.2%～99.2%;日内、日间RSD均<7%。结论:本方法灵敏、稳定、结果准确可靠,可用于二者血药浓度测定。     

改良高效液相色谱法测定血浆中顺铂磁性纳米药物的含量

目的建立高效液相色谱技术测定血浆中顺铂浓度的方法来进行药物代谢动力学的研究。方法用Waters色谱系统。色谱条件:2487双通道紫外检测器。C18色谱柱(大连依利特ODS2分析柱,250mm×4.6mm,5μm),外接菲罗门C18(4mm×4 mm保护柱)。恒温35℃,流速1.0ml·min-1,流动相水-甲醇(28∶72),Waters 1525泵,717自动取样器,进样量为20μl,Breeze色谱工作站。血浆中的顺铂经二乙基二硫代氨基甲酸钠衍生化后,用氯仿提取其产物Pt(DDTC)2,离心后直接取氯仿层进样,采用高效液相色谱仪在254 nm处测定药物浓度。结果本法能有效地测定兔血浆中的顺铂浓度。样品各组分分离良好,顺铂线性范围为0.20768-12.468 mg.L-1,相关系数r=0.9999,日间和日内变异系数均小于10%。结论该方法是一种高效、准确的检测方法,适用于顺铂药物动力学的研究。     

HPLC法测定克林霉素磷酸酯及其有关物质的方法学研究

目的:建立克林霉素磷酸酯及其有关物质含量的测定方法并进行方法学研究。方法:采用HPLC法,色谱柱为Li-chrospher C_(18)柱(250mm×46mm,5μm);柱温:25℃;流动相为0.1mol·L~(-1)的磷酸二氢钾缓冲液(用40％氢氧化钾溶液调节pH=5.6)-乙腈(76:24);流速:1.2mL·min~(-1);检测波长:210nm。结果:与BP1998和EP1997相比,表克林霉素-2-磷酸酯及其另一未知杂质和克林霉素磷酸酯得到很好分离;线性范围;克林霉素-2-磷酸酯在0.1～5.0mg·mL~(-1)呈良好线性,r=0.9996;克林霉素B-2-磷酸酯在0.0013～0.13mg·mL~(-1)呈良好线性,r=0.9981;表克林霉素-2-磷酸酯在0.0014～0.14mg·mL~(-1)呈良好线性,r=0.9972;克林霉素在0.0011～0.11mg·mL~(-1)呈良好线性,r=0.9983;最低检测限为0.1μg;最低定量限为0.33μg。结论:本法比英国药典和欧洲药典更能准确地测定克林霉素磷酸酯及其有关物质含量。     

中药饮片制川乌、制草乌中乌头碱、次乌头碱的HPLC测定

目的:建立一种测定中药饮片制川乌、制草乌中乌头碱、次乌头碱含量的高效液相色谱方法。方法:饮片粉碎成粗粉,用氨试液润湿,乙醚浸提14h,提取液挥弃乙醚,残渣以二氯甲烷溶解,定容至5mL,用0.01mol·L~(-1)H_2SO_4溶液1mL萃取等体积的二氯甲烷液,取水相进样20μL,以Kromasil C_(18)(250mm×4.6mm,5μm)为色谱柱,甲醇-水-氯仿-三乙胺(70:30:2:0.1)为流动相,检测波长230nm,柱温为室温。结果:乌头碱在9.63-96.26μg·mL~(-1),次乌头碱在24.2-242μg·mL~(-1)范围内,线性关系良好(进样量为20μL),方法加样回收率>96%,RSD<2%。结论:该方法准确,精密度高,分离效果好,操作简单。     

RP-HPLC法测定人血浆中氟比洛芬的浓度

目的:建立以反相高效液相色谱法测定人血浆中氟比洛芬浓度的方法。方法:采用外标法,以乙腈沉淀法处理样品后进样测定,色谱柱为Symmetry shield C_(18),流动相为磷酸盐缓冲液(pH7.0):乙腈=75:25,流速为1.0 mL·min~(-1),紫外检测波长为247 nm。结果:氟比洛芬血药浓度在0.05～20μg·mL~(-1)范围内线性关系良好(r=0.999 1),检测限为0.05μg·mL~(-1);低、中、高浓度的回收率在96.1%～107.1%之间,日内及日间RSD均<10%,符合方法学要求。结论:本方法简便、准确、快速,适用于人血浆中氟比洛芬浓度监测及药动学研究。     

高效液相色谱法测定替米沙坦血药浓度

目的:建立测定人血浆中替米沙坦浓度的方法。方法:血浆样品用甲醇提取及沉淀蛋白。采用反相高效液相色谱-荧光法进行分离、测定。色谱柱采用Diamonsil~(TM)C_(18)(200mm×4．6mm,5μm),流动相为水-乙腈-三乙胺(73:27:0．1),柱温25℃,流速为1．0mL·min~(-1),荧光激发波长为305nm,发射波长为380nm。结果:线性范围为1～200ng·mL~(-1)(r=0．9999),最低检测浓度为1．0ng·mL~(-1),高、中、低3种浓度的方法回收率为97%～103%,提取回收率均大于93%。日内及日间精密度均＜7%。结论:本方法简单、快速,灵敏度和准确度较高,能满足替米沙坦临床药动学研究的需要。     

HPLC法同时测定复方单硝酸异山梨酯阿司匹林片含量

目的:建立用高效液相色谱同时测定复方单硝酸异山梨酯阿司匹林片中2种组分和主要降解产物水杨酸含量的方法。方法:采用Hypersil BDS C_(18)(250mm×4.6mm,5μm)色谱柱,流动相:0.02mol·L~(-1)磷酸二氢钾溶液-甲醇(60:40,用磷酸调节pH至2.8±0.1),流速1.0mL·min~(-1),检测波长220nm,柱温40℃,进样量10μL。结果:线性范围分别是:单硝酸异山梨酯0.0119～1.19mg·mL~(-1),r=0.9998(n=6);阿司匹林0.01～1.0mg·mL~(-1),r=0.9996(n=6);水杨酸0.01012～1.012mg·mL~(-1),r=0.9985(n=6)。平均回收率:单硝酸异山梨酯>99.0%,RSD为<1.0%;阿司匹林>99.0%,RSD为<0.9%。结论:本法分离度好,快速,简便。适用于复方制剂中3种组分的同时测定,可作为产品的质量控制方法。     

反相高效液相色谱法测定人体血浆中扑尔敏的浓度

目的:建立一种测定人体血浆中扑尔敏浓度的高效液相色谱法。方法:取人体血浆1.5 mL,加内标右美沙芬后,用三氯甲烷提取,取其有机相于60℃水浴挥干,剩余物加流动相复溶,并用乙酸乙酯洗涤,取水相20μL进样。流动相为0.025mol·L~(-1)磷酸二氢铵(用磷酸调pH为3.5)-乙腈(70:30),色谱柱为Diamonsil ODS C_(18)柱(5μm,4.6mm×150mm),检测波长为200 nm,流速为1.0mL·min~(-1),柱温为室温。结果:本方法线性范围为0.5～16ng·mL~(-1),,r=0.998 7,最低检测限为0.25ng·mL~(-1),方法回收率为96.6％～108.0％,日内RSD为4.1％～5.9％,日间RSD为4.6％～5.9％。结论:本方法灵敏度高,特异性强,重现性好,可用于人体血浆中扑尔敏浓度的测定。     

固相萃取反相高效液相色谱法检测人血浆中辛伐他汀浓度

目的:建立反相高效液相色谱法测定人血浆中辛伐他订。方法:应用OASIS因相萃取小柱提取血浆中辛伐他汀,采用反相高效液相色谱法二极管阵列检测器检测,色谱柱为Symmetry C_(18)柱(250mm×4.6mm,5μm),内标物为洛伐他汀,流动相为0.1％磷酸液(用氢氧化钠调pH4.0)-乙腈(40:60),检测波长238um,流速1.2mL·min~(-1)。结果:辛伐他汀在1.0～35.0ng·mL~(-1)范围内线性良好(r=0.9997)。低、中、高浓度加样回收率在97.3％～108.0％之间,日内、日间RSD在5.9％～8.8％之间,最低检测浓度为0.8ng·mL~(-1)。结论:本法快速、灵敏、高效,适于辛伐他汀的血药浓度检测。     

高效液相色谱—荧光检测法测定异丙酚的血药浓度

目的:建立测定异丙酚血药浓度的方法。方法:应用反相高效液相色谱技术,血浆样品经10％三氯乙酸甲醇溶液沉淀后,离心取上清液,以甲醇-水(85:15)为流动相,流速1mL·min~(-1),进样量50μL,经C_(18)柱分离后,荧光检测,λex=276nm,λem=310nm。结果:在0.1～8.0μg·mL~(-1)浓度范围内,异丙酚峰面积与浓度呈良好的线性关系(r=0.9994)。异丙酚的平均加样回收率大于90％,日内和日间RSD均小于4％。本实验最低检测浓度为0.05μg·mL~(-1),绝对回收率大于70％。结论:本法快速、简便、准确、灵敏,可用于异丙酚的血药浓度监测。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.