高效液相色谱法测定大鼠血浆中凡德他尼的浓度

目的 建立大鼠血浆中凡德他尼的高效液相色谱测定方法,为凡德他尼药代动力学研究提供参考.方法 血浆样品经处理后,采用高效液相色谱法进行分析.Agilent HC-C18柱分离,流动相采用乙腈-0.02 mol/L磷酸二氢钠溶液(80∶20),流速为1 ml/min;利用光电二极管阵列检测器对流份进行检测,柱温30℃.结果 内源性物质不干扰测定,凡德他尼的线性范围为0.5 ～ 10 mg/L(R =0.997),最低定量限值为0.5 mg/L,基质效应为95.2％～103.7％,加样回收率为73.1％ ～87.9％.结论 建立的高效液相色谱方法简便、灵敏、准确、所需样本量小,可为凡德他尼血药浓度检测提供依据.     

Direct high pressure liquid chromatographic analysis and preliminary pharmacokinetics of enantiomers of oxazepam and temazepam with their corresponding glucuronide conjugates

Three high pressure liquid chromatographic systems for the separation of oxazepam, temazepam and their glucuronides (system A), the separation of theirR,S glucuronide diastereomers (system B) and the chiral separation of the parent drugs (system C) are described. Preliminary pharmacokinetics ofR,S-oxazepam andR,S-temazepam in a human volunteer reveal that the protein binding of the glucuronides is lower than that of the parent drugs, but that there is no difference in protein binding between theR-oxazepam/temazepam andS-oxazepam/temazepam and their corresponding glucuronides. TheS-glucuronide is the main metabolite formed and excreted by man. The plasma ratioR/S-glucuronide is 11 for both oxazepam and temazepam. The renal clearances ofR-temazepam, andS-temazepam are similar, and those ofR-oxazepam andS-oxazepam tend to be different.     

High pressure liquid chromatographic analysis and preliminary pharmacokinetics of sulfaphenazole and its N2-glucuronide and N4-acetyl metabolites in plasma and urine of man

A direct high pressure liquid chromatographic analysis of sulfaphenazole-N2-glucuronide in urine is described. After an oral dose of 439 mg of sulfaphenazole, 0% is excreted unchanged in the urine, < 1% is excreted as N4-acetylsulfaphenazole. As N2-glucuronide 49.4% is excreted in one slow acetylator and 84.8% in one fast acetylator.     

Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates

The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients under combined general and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphine could be detected in the serum. Morphine appeared almost instantaneously with a lag-time of 8 min and had a final elimination half-life of 1.48±0.48 h. Morphine was metabolized to morphine-3-glucuronide and morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide conjugates was similar: about 2.8 h (P>0.8). The glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphine was 162 m·min^–1 and for the glucuronides 81 ml·min^–1. This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbed and immediately hydrolysed to morphine.     

法莫替丁肠溶片的血浓度测定及其在人体的药代动力学研究

目的研究法莫替丁的血药浓度测定方法,并应用其进行法莫替丁片剂的人体药代动力学研究。方法采用固相萃取—高效液相色谱(HPLC)紫外检测法测定法莫替丁的血药浓度。18名健康男性志愿者,单剂量口服40mg法莫替丁片剂,不同时间点取静脉血,由血药浓度数据计算各自的主要药代动力学参数。结果所建立的血药浓度测定法能满足药代动力学实验要求。单次服用40mg法莫替丁片剂的主要药代动力学参数血药浓度-时间曲线下面积(AUC)0→12、AUC0→∞、Cmax、Tmax、T1/2分别为(882±185)、(912±187)ng·ml-1·h-1、(171±33)ng/ml、(2.3±0.4)和(2.6±2.7)h。结论法莫替丁的血药浓度测定方法简单、可靠。所得的药代动力学参数与国内外文献报道相似。     

高效液相色谱法测定接骨续筋胶囊中柚皮苷的含量

目的建立高效液相色谱法测定接骨续筋胶囊中柚皮苷含量的方法。方法采用Hypersil BDS C18柱(4.6mm×250mm,10μm);流动相:甲醇-醋酸溶液(38∶62);流速:1.0ml/min;检测波长:283nm;柱温:40℃;进样量:10μl。结果柚皮苷线性范围为0.1535～0.7675μg(r=0.9999);平均加样回收率为99.1%,相对标准偏差(RSD)为0.67%。结论该方法简便、快速、准确,可用于接骨续筋胶囊中柚皮苷的含量测定。     

高效液相色谱法测定消渴降糖胶囊中槲皮素的含量

目的建立消渴降糖胶囊中槲皮素含量测定的方法。方法采用高效液相色谱法,色谱柱为Kromasil-C18(4.6mm×250mm,粒径5μm),甲醇-0.2%磷酸溶液(48:52)为流动相,检测波长360nm,流速1.2ml/min,柱温40℃。结果槲皮素在26.24～131.2μg/ml范围内,浓度与峰面积呈线性关系(r=0.9989)。平均加样回收率为100.0%(RSD=3.10%)。结论该方法简单、准确、可靠、专属性强、重现性好,可作为消渴降糖胶囊的质量控制方法。     

反相高效液相色谱法测定大鼠血浆中补阳还五汤总生物碱中川芎嗪的含量及药代动力学研究

目的对大鼠血浆中补阳还五汤及总生物碱中川芎嗪的含量进行了测定,并对其药代动力学研究。方法采用反相高效液相色谱(RP-HPLC)法测定,其条件为色谱柱:C18柱,4.6mm×250mm,5μm;检测波长:278nm;流动相:甲醇∶水(33∶67);流速:1ml/min;柱压:(20.7±0.4)MPa;温度:35℃。药代动力学参数采用3P87软件处理。结果血浆样品中川芎嗪线性范围为51.4￣308.4ng,r=0.9997,回收率为98.85%,sx为1.492%。川芎嗪药代动力学参数:复方:t1/2α为27.73min,t1/2β为8197min;k12为0.02067min-1,k21为0.003860min-1,k10为0.0005470min-1;总生物碱:t1/2α为27.72min,t1/2β为9043min;k12为0.02135min-1,k21为0.003117min-1,k10为0.0006120min-1。结论该法快速、简便,准确。补阳还五汤复方及总生物碱中川芎嗪药代动力学为二室模型。中药复方成分组合对药代动力学参数有一定影响。     

高效液相色谱法测定人血浆中阿莫地喹的浓度(英文)

目的:建立高效液相色谱法测定人血浆中阿莫地喹的浓度。方法:分析柱采用KromasilC18(150mm×4.6mm,5μm),流动相为甲醇∶水∶三乙胺∶磷酸∶(21∶77.5∶1∶0.5),流速为1.0mL·min-1,检测波长为294nm,内标为羟氯喹。结果:阿莫地喹和羟氯喹的保留时间分别为5.82min,8.56min。该法在10～1000μg·L-1浓度范围内有良好的线性关系(r=0.9998,n=9),最低检测限为5μg·L-1,提取回收率为75.5%～82.7%,方法回收率为97.0%～104.8%。日内精密度的RSD<6.0%,日间精密度的RSD<7.5%。结论:该法简单,灵敏适合于阿莫地喹的药动学研究。     

高效液相色谱法测定注射用法罗培南在健康人血浆和尿中的浓度

目的:建立测定人血浆和尿中注射用法罗培南浓度的高效液相色谱(HPLC)法。方法:血浆样品经10%三氯醋酸沉淀蛋白,尿样直接稀释,以替硝唑为内标,采用乙腈:0.05 mol·L~(-1)磷酸二氢钾缓冲液(pH 3.5,16:84,V:V)为流动相,经Zorbax XDB-C_8柱分离,318 nm波长检测。结果:法罗培南的血浆样品和尿样线性范围分别为0.1～50 mg·L~(-1)和0.5～250 mg·L~(-1),提取回收率分别为51.2%～54.9%和99.6%～104%,日内、日间精密度(RSD)均低于9.14%。结论:本方法准确性好、操作简单,可满足药动学研究的要求。     

高效液相色谱法测定阿伐斯汀在小猎兔犬的血药浓度

目的:建立测定Beagle(小猎兔)犬血浆中阿代斯汀药物浓度的测定方法。方法:Beagle犬单次经口给予阿代斯汀胶囊8 mg后,以高效液相色谱法测定其血药浓度,采用DASv2．0软件拟合其药动学参数。结果:阿伐斯汀的血药浓度范围在3．4～572μg·L~(-1)内线性关系良好;定量限为3．4μ,g·L~(-1),日内和日间误差均不超过15％。结论:高效液相色谱法测定阿伐斯汀血药浓度,方法简单、准确,可以用于阿伐斯汀在Bealge犬的药动学研究。     

猪凝血酶中右旋糖酐20含量测定的高效液相色谱法建立及验证

目的:建立测定猪凝血酶中右旋糖酐20含量的高效液相色谱法,并对方法进行验证和初步应用。方法:根据分子排阻色谱法,以亲水硅胶高效体积排阻色谱柱进行分离,采用示差折光检测器测定右旋糖酐20含量。应用该方法对3批猪凝血酶样品中右旋糖酐20含量进行检测。结果:该方法专属性强,线性范围为2.314～7.406 mg/ml;低、中...     

高效液相色谱法测定人血浆中咪唑立宾的浓度

目的：建立测定人血浆中咪唑立宾的高效液相色谱法。方法：样品预处理采用乙腈蛋白沉淀法。色谱柱为Phenomenex Luna NH_2(4．6 mm×250 mm,5μm)；流动相为乙腈-甲醇-0．1%三氟乙酸(85∶5∶10,V∶V∶V)；流速为1．5 mL·min~(-1)；柱温为30℃；紫外检测波长为280 nm。结果：血浆内源性杂质和常用合并用药对待测物的测定无干扰。咪唑立宾的线性范围为0．1～10 mg·L~(-1)；日内、日间RSD均小于9%；样品3次冻融,以及在提取前后4℃下24 h内稳定性均良好。结论：该法快速、灵敏、准确,可用于咪唑立宾的药动学研究及常规治疗药物监测。     

高效液相色谱法测定五味消毒饮中绿原酸含量

目的建立测定五味消毒饮中绿原酸含量的高效液相色谱法。方法高效液相色谱法测定五味消毒饮中绿原酸的含量,采用色谱柱：Hypersi1OD色谱柱（4．6mm×250．0mm,5μm）;流动相：乙腈-0．4％磷酸水溶液（12：88,体积比）;流速：1．0mL／min;检测波长：327nm;柱温：30℃。结果绿原酸含量在0．0000-0．5540μg时呈良好的线性关系,回收率为101．2%,相对标准偏差为0．34％（n=6）。结论该方法简便,重复性好,可作为五味消毒饮中绿原酸含量的检测方法。     

HPLC法测定人血浆中伊曲康唑的含量及其药代动力学研究

目的建立HPLC法测定人血浆中伊曲康唑含量方法及药代动力学特征的研究。方法选取20名健康受试者高脂饮食后随机交叉口服受试制剂和参比制剂伊曲康唑片100mg。采用HPLC-UV法测定伊曲康唑的血药浓度。结果受试制剂的相对生物利用度为(99.7±9.2)%。结论伊曲康唑的药代动力学特征较明显,表明两制剂具有生物等效性。     

High pressure liquid chromatographic analysis of the serum concentration of cefuroxime after an intravenous bolus injection of cefuroxime in patients with a coronary artery bypass grafting

A simple reversed-phase high pressure liquid chromatographic method was developed for the determination of cefuroxime in the serum of patients undergoing coronary artery bypass grafting. The serum was cleaned up with a 3.3% solution of perchloric acid in water.Cefalexine was used as an internal standard. Detection was made by a UV multi-wavelength detector. The optimum wavelength for cefuroxime is 275 nm. The absolute recovery of this method was 90.9%; the limit of quantification was 0.7 mg/l. This analytical method was used in a study to investigate the cefuroxime serum concentration-time curves in 26 patients undergoing coronary artery bypass grafting. It was found that one single dose is sufficient to obtain effective serum concentrations.     

Interindividual variation in the capacity-limited renal glucuronidation of probenecid by humans

A dose of 1,000 mg probenecid was administered orally to 14 human volunteers in order to quantify the maximal rate of formation and excretion of probenecid acyl glucuronide in the urine. Probenecid showed dose-dependent pharmacokinetics. Plasma protein binding of probenecid was high, being somewhat higher in males (90.7±1.4%) than in females (87.9±1.4%; p=0.0019). It was shown that probenecid is metabolized by cytochrome P-450 into at least two phase I metabolites. Each of the metabolites accounted for less than 12% of the dose administered; the main metabolite probenecid acyl glucuronide, representing 42.9±13.2% of the dose, was only present in urine and not in plasma. The renal excretion rate-time profile of probenecid acyl glucuronide showed a plateau value in the presence of an acidic urine pH. This plateau value was maintained for about 10 h at the dose of 1,000 mg. The height of the plateau value depended on the individual and varied between 250 and 800g/min (15–50 mg/h). It was inferred that probenecid acyl glucuronide is formed in the kidney during blood-to-lumen passage through the tubular cells. We conclude that the plateau value in the renal excretion rate of probenecid glucuronide reflects itsV _max of formation.     

液相色谱法测定吗氯贝胺及其多剂量口服后在人体的药动学(英文)

目的 :建立人血浆中吗氯贝胺的反相高效液相色谱检测方法 ,并研究中国健康男性志愿者多剂量口服吗氯贝胺后的药动学特征。方法 :采用反相高效液相色谱法测定人血浆中吗氯贝胺含量。血浆样品在碱性条件下 (pH 11)用二氯甲烷提取处理。色谱柱为 μ BondapakTM C18(12 5 ,10 μm ,3.9mm× 15 0mm)。流动相为乙腈 :0 .0 6 7mol·L- 1磷酸二氢钾溶液 (1∶5 ,V/V ,pH 2 .6 ) ,2 4 0nm检测。内标为甲氧氯普胺。应用 3P97程序拟合药动学参数。结果 :吗氯贝胺在 4 0～ 4 0 0 0 μg·L- 1范围内线性关系良好 (r =0 .9999) ,方法回收率在 99%～10 3%之间 ,日内日间RSD小于 8.14 %。吗氯贝胺血药浓度 时间曲线符合一室模型 ,主要稳态药动学参数Cmax为 (3911± 14 2 ) μg·L- 1;Tmax为 (1.4 2± 0 .2 0 )h ;T1/2 (kel) 为 (2 .6± 0 .3)h ;AUC0 2 4 为(2 2 5 83± 182 1) μg·h·L- 1;MRT为 (4.76± 0 .2 5 )h ;CL/F(s) 为 (2 1.2± 1.2 )L·h- 1。结论 :该方法快速、准确、灵敏度高、专属性强 ,可应用于吗氯贝胺的血药浓度测定     

高效液相色谱法测定炔丙基半胱氨酸及其有关物质的含量

目的建立高效液相色谱法测定炔丙基半胱氨酸(SPRC)及有关物质的含量。方法采用Welchrom-AQ C18色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-离子对缓冲液(10 mmol.L-1庚烷磺酸钠+20 mmol.L-1KH2PO4,H3PO4调pH至2.4)(10∶90,V/V),紫外检测波长210 nm,流速1.0 mL.min-1。结果 SPRC在5.0～25.0 mg.L-1范围内具有良好的线性关系(r=0.999 5),最低检测限0.2 mg.L-1;样品溶液在24 h内稳定,精密度良好(<1.0%),回收率在98.0%～100.0%之间,3批样品的标示百分含量分别为96.94%、96.67%和96.56%,有关物质的含量分别为3.20%、3.43%和3.65%。结论本方法简便、灵敏,结果可靠准确,可用于SPRC及其有关物质的含量测定。