高效液相色谱法测定人血浆中奥美拉唑浓度

建立测定人血浆中奥美拉唑浓度的高效液相色谱法,并应用于人体药代动力学研究。血浆样品中加入内标非那西丁后用乙酸乙酯提取,色谱柱为ZorbaxSB-C18柱,流动相为0·05mol·L-1乙酸铵溶液(用氨水调至pH7·0)-乙腈(68∶32),流速为1·0ml·min-1,紫外检测波长302nm。血浆中内源性物质对样品测定无干扰。本方法线性范围为0·01~2μg·ml-1(r=0·9997),最低定量浓度为0·01μg·ml-1,提取回收率大于80%,方法回收率为98·6%~103·1%,日内、日间RSD均小于6%。本法简便、准确,适用于奥美拉唑药代动力学的研究。     

高效液相色谱法快速测定人血浆中格列喹酮浓度及药动学研究

目的：建立一种简单快速测定人血浆中格列喹酮浓度的高效液相色谱法,并用于格列喹酮片的药动学研究。方法：采用乙腈直接蛋白沉淀法处理血浆样本,建立高效液相色谱-荧光检测法测定血浆样本中格列喹酮的浓度。流动相为乙腈-20mmol·L-1磷酸二氢钾（80∶20,v/v,pH 2.5）,流速为1.0 ml·min^-1。荧光检测器：激发波长315 nm,发射波长410 nm。结果：血浆格列喹酮浓度在0.034-2.2μg·ml^-1范围内呈良好的线性,定量下限为0.034μg·ml^-1。方法回收率99.23%-108.11%,提取回收率85.78%-88.77%,日内、日间精密度均〈10%,特异性、稳定性考察均符合要求。应用本法测定20名健康受试者单次口服60 mg格列喹酮片的血浆药物浓度并计算主要药动学参数,变异系数均接近或大于50%。结论：该方法简便快速、灵敏度高,可用于大批量测定格列喹酮的血药浓度;格列喹酮药动学参数的个体差异较大,临床需注意个体化用药。     

高效液相色谱法测定人血浆中法莫替丁浓度及药动学研究

目的:建立人血浆中法莫替丁浓度的高效液相色谱测定方法,并用于药动学研究.方法:9名健康男性志愿者单剂量口服法莫替丁胶囊40 mg,给药后不同时间采集血样,1 mL血浆样品以乙酸乙酯提取,采用反相高效液相-二极管阵列检测器分离测定血浆中的法莫替丁浓度,以3P97程序计算其药动学参数.结果:法莫替丁检测浓度线性范围为12.5～400μg·L-1(r=0.999 6),最低定量限为12.5μg·L-1.高、中、低浓度的方法回收率分别为98.98%,99.16%,104.49%,日内及日闻RSD均小于15%.药动学研究表明,法莫替丁的药-时曲线符合-室模型.结论:本方法准确度好,灵敏度高、稳定、简便,适用于法莫替丁血药浓度测定及其药动学研究.     

HPLC法测定围手术期患儿血浆中瑞芬太尼浓度

目的:建立高效液相色谱法测定围手术期患儿血浆瑞芬太尼浓度.方法:采用Hypersil CN柱(250 mm×4.6 mm,5μm);流动相为乙腈-0.02 mol·L-1磷酸二氢钾水溶液内含三乙胺0.02%(30:70);流速1.0 ml·min-1;检测波长210nm;进样量为20 μl.结果:标准曲线在1.0～100.0 μg·L-1 内线性关系良好(r=0.999 3).最低检测浓度为1.0μg·L-1.提取回收率(76.51±0.82)%.方法回收率99.66%～102.40%.日内和日间RSD均小于15%.2μg·L-1组靶控浓度与实测浓度基本一致.结论:本方法快速、准确、灵敏、专一性好,适用于临床瑞芬太尼血药浓度检测和药动学研究.     

高效液相色谱法测定奥硝唑的血药浓度及其人体药动学研究

目的:建立奥硝唑血浆浓度测定的反相高效液相色谱法,并用此法研究奥硝唑人体药动学.方法:采用Hypersil ODS色谱柱(250mm×4.6mm,10μm);以甲醇-0.01mol·L-1磷酸二氢钠(40∶60)为流动相,流速为1mL·min-1,检测波长318nm,甲硝唑作内标.结果:奥硝唑在0.5～32.0μg·mL-1浓度范围内呈线性,r=0.998 8.最低定量浓度0.5μg·mL-1.低、中、高浓度(1.0,8.0,32.0μg·mL-1)的方法回收率分别为86.2%,97.2%,96.8%;萃取回收率分别为73.8%,90.8%,92.9%,日内RSD<8%,日间RSD<11%.药动学研究表示,口服奥硝唑胶囊与片剂的药-时曲线均符合一级吸收、一级消除的一房室模型.结论:该法准确可靠,操作简便,适用于临床药动学研究及血药浓度监测.     

固相萃取HPLC测定人血浆中头孢西酮及在药动学研究中的应用

目的:建立反相高效液相色谱办法测定人血浆中头孢西酮浓度,并用于注射用头孢西酮钠人体药代动力学研究。方法:采用高效液相色谱紫外检测法,血浆中加入内标后经固相萃取,色谱柱为 Apollo C_(18)(5μm,250 mm×4.6 mm)。流动相为乙腈-0.02 mol·L~(-1)醋酸铵溶液(18∶82)(pH 5.0),流速1 mL·min~(-1),检测波长为278 nm。结果:本方法线性检测范围为0.5～250μg·mL~(-1),线性关系良好(r=0.9996);最低检测浓度为0.5μg·mL~(-1);方法绝对回收率为67.2%～84.0%,相对回收率为91.1%～102.1%;日内、日间 RSD 均小于8%。结论:本方法灵敏度高,操作简便,可用于人血浆中头孢西酮的浓度测定及临床药代动力学研究。     

高效液相色谱法同时测定人血浆中对乙酰氨基酚、伪麻黄碱和咖啡因

目的:建立一种同时测定人血浆中对乙酰氨基酚、伪麻黄碱和咖啡因的高效液相色谱(HPIC)法,并用于含上述组分的复方制荆的人体药动学研究.方法:以荼碱为内标,血样经醋酸乙酯提取后,采用高效液相色谱紫外(HPLC_UV)法进行测定.色谱柱为Diamonsil C<,18>柱(4.6 mm x 150mm,5μm);流动相为甲醇-0.05 mo·L-1磷酸二氢钾(23:77,pH 2.4);流速1 mL·min-1.检测波长210 nm.结果:人血浆中对乙酰氨基酚、盐酸伪麻黄碱和咖啡因质量浓度测定的线性范围分别为0.12～11.52 mg·L-1,0.008～0.432mg·L-1和0.03～2.16mg·L-1;最低可定量质量浓度分别为0.12,0.008,0.03 mg·L-1;各组分日内、日间RSD均小于15%,方法回收率均大于88%.结论:该方法能快速可靠地同时测定人血浆中对乙酰氨基酚、伪麻黄碱和咖啡因的浓度.可用于含上述组分的复方制剂的人体药动学或生物等效性研究.     

高效液相色谱法测定西罗莫司血药浓度

目的:建立快速测定人全血中西罗莫司浓度的高效液相色谱方法.方法:色谱柱为Zorbax Eclipse XDB C18(4.6mm×150mm,5μm);流动相为甲醇-乙腈-去离子水(50∶22∶28,v/v);流速1.2mL·min-1;紫外检测波长278nm;柱温50℃.结果:西罗莫司浓度测定的线性范围为2.5～50.0μg·L-1,最低检测浓度为2.0μg·L-1,平均回收率为103.2%,日内RSD小于5%,日间RSD小于4%.结论:本方法简便、快速,定量准确,可用于西罗莫司临床药动学研究,也可用于西罗莫司常规血药浓度监测.     

高效液相色谱法测定血浆中西洛他唑浓度及药动学

目的:建立测定血浆中西洛他唑浓度的高效液相色谱法,考察西洛他唑在中国健康志愿者体内的药动学行为.方法:血浆样品经液-液提取后,进行色谱分离测定.结果:西洛他唑的最低定量浓度为25.0μg·L-1,线性范围为25.0～2000.0μg·L-1,精密度与准确度符合生物样品分析要求.结论:该法操作简便、快速、灵敏度高.可检测出健康志愿者口服100 mg西洛他唑72 h后的血浆浓度,适于临床药动学研究.     

高效液相色谱-质谱法研究甘草酸二铵胶囊在健康人体的药代动力学

目的建立人血浆中甘草次酸的高效液相色谱-质谱测定法,并研究其在健康志愿者的药代动力学。方法口服甘草酸二铵胶囊(抗炎保肝药)100mg后,血样经乙酸乙酯提取后,进行LC-MS分析,色谱柱为LichrospherODS(5μm,100mm×4.6mm),流动相为乙腈-10mmol·L-1醋酸铵水溶液(90∶10),内标为熊果酸,检测离子为m/z469.5(甘草次酸)、m/z455.5(内标),裂解电压为200V。测定甘草次酸的血药浓度,计算其药代动力学参数。结果在0.1~400μg·L-1内,甘草次酸与内标的峰面积比值与浓度的线性关系良好,定量限为0.1μg·L-1,提取回收率为88.0%~98.0%。人体中甘草次酸药代动力学参数:Cmax为(65±26)μg·L-1,tmax为(11.5±2.3)h,t1/2为(8.0±2.2)h,AUC0-48为(1006±426)μg·h·L-1。结论本方法灵敏、准确、简便,适于临床药代动力学研究。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.