高效液相色谱法测定头孢克罗血浆浓度及其药动学研究

本文用离子对高效液相色谱法（ＨＰＬＣ）测定血浆中的头孢克罗（Ｃｅｆａｃｌｏｒ）浓度。血浆样品用１％磷酸甲醇溶液提取。色谱条件为：紫外检测波长λ２６５ｎｍ；分析柱ＵｌｔｒａｓｐｈｅｒｅＴＭ“ＩＰ”２５０ｍｍ×４．６ｍｍ；流动相甲醇：四氢呋喃：水（每升水中含１．０ｇ庚磺酸钠，１１ｇ三乙胺，２０．５ｇ磷酸）。本法最小检测限５０ｎｇ／ｍｌ。本法对１０名受试者口服２５０ｍｇ头孢克罗后进行药动学和相对生物利用度研究。头孢克罗为一房室模型，其Ｔ１／２（ｋｅ）０．６ｈ，Ｔｍａｘ０．４～０．７ｈ，Ｃｍａｘ４．９２～６．５０μｇ／ｍｌ。颗粒剂的相对生物利用度为１．０７±０．１３。     

高效液相色谱法测定入血浆中氟西汀浓度

目的建立测定人血浆中氟西汀浓度的高效液相色谱法。方法以DiamonsilTMC18反相柱（150mm×4．6mm,5μm）为色谱柱,流动相为0．03mol·L-1醋酸铵．甲醇（27：73）;流速：0．8mL·min-1;柱温：40℃;检测波长：260nm。以乙酸乙酯与二氯甲烷（80：20）为提取剂。结果氟西汀的低、中、高（10．0。40．0。320．0ng·mL-1）3种浓度平均回收率分别为101．56％,98．61％。97．92％。提取回收率分别为71．12％,73．71％,76．59％;日内、日间差RSD均低于9％（n=5）;分析方法的检测限为5．0ng·mL-1;线性范围为10．0--320．0ng·mL-1。线性方程：Y=98．12X＋1．71．r=0．9989（n=8）。结论该方法灵敏、准确、简单、快速,可用于氟西汀临床血药浓度监测和药动学研究。     

高效液相色谱法测定人血浆中氟西汀的浓度

氟西汀(Fluoxetine)是一种5-羟色胺重摄取抑制剂,由于没有抗胆碱作用及心血管副作用,临床上广泛用于抑郁症、强迫症和神经性贪食的长期治疗.     

磷酸西他列汀在大鼠体内的药代动力学研究

目的:建立超高效液相色谱-电喷雾离子源-串联三重四极杆质谱(UHPLC-ESI-MS/MS)方法测定大鼠血浆中磷酸西他列汀的含量,研究磷酸西他列汀经尾静脉单次给药后在SD大鼠体内的药代动力学过程。方法:18只SD大鼠分为3组,分别单次给予9,3,1 mg.kg-1磷酸西他列汀,按照不同时间点于眼后静脉丛采血。液质联用法测定血药浓度。质谱采用正离子和选择反应监测(SRM)模式,用于定量分析的离子分别为磷酸西他列汀m/z 408.0→235.0和内标氟西汀m/z 310.0→148.0。根据非房室统计矩模型用WinNolin软件进行曲线拟合并计算药代动力学参数。结果:大鼠分别尾静脉单次注射高、中、低剂量(93,和1 mg.kg-1)药物后,血药浓度-时间曲线下面积(AUCINF)分别为(5 154.82±637.37)(,1 729.30±290.76)和(589.39±66.92)h.ng.mL-1,剂量之比为9∶3∶1,对应的AUC比值为8.75∶2.93∶1,与给药剂量呈线性正相关性;统计结果表明3个剂量组的AUC有显著性差异t,1/2,Vz,CL,MRTlast与给药剂量无关。结论:所建立的UHPLC-M...     

高效液相色谱法测定人血浆中西洛他唑药物浓度及药动学研究

目的建立高效液相色谱法测定人血浆中西洛他唑的浓度,并研究其在健康人体内的药动学。方法采用C18反相色谱柱,以乙腈-水(0.1%甲酸)(65∶35)为流动相等度洗脱,流速为1.0 mL·min-1;检测波长为257 nm;进样量为20μL。结果西洛他唑在0.05～10 mg·L-1范围内线性关系良好(r=0.999 8),各样品的提取回收率均大于80%,日内、日间精密度RSD均小于10%。西洛他唑的血药经时过程符合一级吸收的二室模型,其主要药动学参数:tmax:2.94±1.21 h;Cmax:(0.99±0.12)mg·L-1;AUC(0-t):(9.57±1.31)mg·h-1.L-1。结论该方法方便快捷,专属性强,准确可靠,适用于西洛他唑的临床药动学研究。     

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.     

高效液相色谱法测定盐酸环丙沙星血药浓度及其药动学研究

采用高效液相色谱法（ＨＰＬＣ）测定盐酸环丙沙星的血药浓度。色谱条件为：紫外检测波长λ２７７ｎｍ；分析柱为ＨＰ－ＲＰ－ＯＤＳＣ１８柱，Φ４．６×２２０ｍｍ；流动相：乙腈∶（溴化四丁基铵０．００８ｍｏｌ·Ｌ－１＋磷酸二氢钾水溶液０．０１１ｍｏｌ·Ｌ－１）＝１４∶８６，配好后磷酸调ｐＨ至２．７４±０．０２。本法血清最低检出浓度０．０１μｇ·ｍｌ－１。对１０名受试者口服５００ｍｇ两种盐酸环丙沙星片后进行药动学和生物利用度研究。药－时曲线经拟合为二室开放模型，其Ｔ１／２β分别为４．６８±０．５３ｈ与４．４０±０．４７ｈ，Ｔｍａｘ分别为１．２８±０．０７ｈ与１．３３±０．０７ｈ，Ｃｍａｘ分别为６．４４±０．６１（μｇ·ｍｌ－１）与５．８８±０．４０（μｇ·ｍｌ－１），ＡＵＣ分别为１９．８８±１．８３（μｇ·ｈ－１·ｍｌ－１）和１９．２４±１．０８（μｇ·ｈ－１·ｍｌ－１）。供试品片剂的相对生物利用度为１０３．３２±４．８１％（９９．５８±４．６３％，经含量校正），经统计分析两种制剂具有生物等效性。     

高效液相色谱法检测人血浆中氟西汀及其代谢产物的浓度

目的 :建立一种快速测定人血浆中氟西汀及其代谢产物去甲氟西汀的反相高效液相色谱法。方法 :用正己烷 -乙腈(98∶2 )提取血浆样品中氟西汀、去甲氟西汀及氯丙帕明 (内标 ) ,在EclipseXDB -C8柱上 ,以 0 0 5mol·L-1磷酸二氢钾 -乙腈 -甲醇 (5 5∶40∶5 )为流动相进行分离 ,流速 1 2mL·min-1,于 2 2 6nm检测。结果 :线性范围为 10～ 5 0 0ng·mL-1,氟西汀和去甲氟西汀相对回收率分别为 99 1%～ 10 4 2 %和 98 2 %～ 10 0 3 % ,日内RSD分别为 4 1%～ 4 8%和 4 5 %～5 8% ,日间RSD分别为 3 5 %～ 5 9%和 4 9%～ 6 8%。结论 :本法简便、精密度高、重现性好 ,结果准确可靠。     

反相高效液相色谱法测定人血浆中倍他司汀浓度

目的:建立以反相高效液相色谱法测定人血浆中倍他司汀浓度的方法。方法:色谱柱为C18,检测波长为261nm,流动相为0.05mol/L乙酸胺-乙腈-0.3mol/L十二烷基硫酸钠(60∶40∶1.5),流速为0.5ml/min。结果:倍他司汀检测浓度在24~480ng/ml范围内线性关系良好,提取回收率在81.75%~87.99%之间,日内和日间RSD分别为0.60%~4.82%和4.78%~12.15%。结论:本方法操作简便、快速、准确、重现性好,适用于人体倍他司汀的药动学研究。     

利巴韦林的含量测定以及人体药代动力学分析

本文建立了简单、快速的HPLC方法测定利巴韦林在人血浆中的含量, 并研究了健康受试者体内利巴韦林片剂的药代动力学。HPLC方法选择C18色谱柱（250mm×4.6mm,5μm）, 超纯水为流动相, 柱温为25°C, 检测波长为207nm。在50.4-2016.0ng/mL范围内线性关系良好（r=0.9998）, 最低检测浓度为15ng/mL。低、中、高三个浓度的相对回收率大于90%, 日内精密度小于10%, 日间精密度小于15%。用药代动力学软件WinNonlin进行房室模型分析的结果显示：二室模型能更好地模拟利巴韦林在体内的过程。计算得到的AUC0-t、CL/F和Cmax分别是10807.8 h·ng/mL、64879.5 mL和525.1ng/mL。这些结果为药剂工作者开发利用利巴韦林剂型提供了参考。     

Determination of SNX-2112, a selective Hsp90 inhibitor,in plasma samples by high-performance liquid chromatography and its application to pharmacokinetics in rats

A sensitive and specific reversed-phase high-performance liquid chromatography method with ultraviolet detection has been developed and validated for the identification and quantification of SNX-2112 in rat plasma. Following sample preparation using liquid–liquid extraction, the analytes were separated by the mobile phase acetonitrile–water (40:60, v/v) with an Agilent RP-HPLC column (ZORBAX SB-C18, 5 μm, 4.6 mm × 250 mm) at a flow rate of 1 ml/min, column temperature of 30 °C and detection wavelength of 251 nm. The retention time of SNX-2112 was 11.2 min. A good linear relationship was obtained in the concentration range studied (0.07–21 μg/ml, R² > 0.9982), and the LLOD and LLOQ for SNX-2112 were 0.02 and 0.07 μg/ml, respectively. The mean absolute recovery of SNX-2112 in plasma ranged from 88.58 to 99.61% at the studied concentrations. The intra- and inter-batch relative standard deviations were 1.7–3.5 and 1.9–4.4%, respectively. This method was successfully applied to pharmacokinetic studies in rats after intravenous administration of SNX-2112.     

Gradient high-performance liquid chromatography for the simultaneous determination of chlorogenic acid and baicalin in plasma and its application in the study of pharmacokinetics in rats

A novel HPLC-UV method was developed for the simultaneous determination of two major active components in Yinhuang injection, chlorogenic acid and baicalin, in rat plasma. Extracted from the plasma samples with methanol-acetonitrile (3:1, v/v), the two compounds were successfully separated using a C18 column with a gradient elution composed of 15 and 54% methanol-acetonitrile (1:1, v/v) in 0.2% (v/v) phosphoric acid water solution (pH 2.0). The flow-rate was set at 1 ml min(-1) and the eluent was detected at 327 nm for chlorogenic acid, 278 nm for baicalin. Puerarin and rutin were used as the internal standards for chlorogenic acid and baicalin, respectively. The method was linear over the range of 0.388-12.4 microg ml(-1), 0.485-124 microg ml(-1) for chlorogenic acid and baicalin, respectively. The correlation coefficient for each analyte was above 0.998. The intra-day and inter-day precisions were better than 7 and 9%, with the relative error ranging from -9.5 to 7.3% and from -4.2 to 1.8%. The limit of detection (LOD) and the limit of quantification (LOQ) for chlorogenic acid and baicalin in plasma were 0.194, 0.122, 0.388 and 0.485 microg ml(-1), respectively. This assay has been successfully applied in the pharmacokinetic study of chlorogenic acid and baicalin in vivo through intravenous administration of Yinhuang injection to rats.     

Development of a high performance liquid chromatography method for quantification of PAC-1 in rat plasma

A sensitive and specific high performance liquid chromatography method with UV detection was developed and validated for the determination of PAC-1 in rat plasma. After extraction with ethyl acetate, the chromatographic separation was carried out on a Diamonsil C₁₈ column (150 mm × 4.6 mm i.d., 5 μm particle size, Zhonghuida) protected by a ODS guard column (10 mm × 4.6 mm i.d., 5 μm particle size), using acetonitrile–methanol–phosphate buffer (pH 3.0, 30 mM) (31:3:66, v/v/v) as mobile phase at a flow rate of 1.0 mL/min, and wavelength of the UV detector was set at 281 nm. No interference from any endogenous substances was observed during the elution of PAC-1 and internal standard (IS, indapamide). The calibration curve was linear over the range of 0.05–20 μg/mL (r > 0.99). The lower limit of quantification was evaluated to be 50 ng/mL. The method was successfully applied to the pharmacokinetic study of PAC-1 after intravenous and oral administration in rats, respectively.     

Development and validation of a high-performance liquid chromatographic method for determination of pinocembrin in rat plasma: Application to pharmacokinetic study

A sensitive and specific reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-UV-HPLC) method has been developed and validated for the identification and quantification of pinocembrin in rat plasma using chrysin as the internal standard. Following protein precipitation with acetonitrile, the analytes were separated by the mobile phase 0.01 M ammonium acetate (pH 4.0)–methanol (35:65, v/v) with an Agilent TC-C18 column (5 μm, 4.6 mm × 150 mm) at a flow rate of 1 ml/min, column temperature 40 °C and detection wavelength 290 nm. A good linear relationship was obtained in the concentration range studied (0.07–133.33 μg/ml, r = 0.9995). The lowest limit of quantification (LLOQ) was 66.7 ng/ml and the lowest limit of detection (LLOD) was 25 ng/ml. Average recoveries ranged from 93.9 to 97.8% in plasma at the concentrations of 0.33 and 33.33 μg/ml. Intra- and inter-batch relative standard deviations were 0.15–2.03 and 1.18–9.96%, respectively. This method was successfully applied to the pharmacokinetic studies in rats after intravenous administration of pinocembrin.     

高效液相色谱法测定大鼠血中头孢他啶浓度的实验

本文报告采用高效液相色谱法（ＨＰＬＣ）测定大鼠血中的头孢他啶浓度。样品在酸性条件下转入水相，样品中杂质在中性条件下转入混合溶媒。色谱柱为ＹＷＧ－Ｃ１８柱，内标物选用氢氯噻嗪。流动相为０．１ｍｏｌ·Ｌ－１醋酸铵缓冲液（ｐＨ４．５９）与甲醇按８８∶１２配成的混合液。最低检出浓度为０．２μｇ·ｍｌ－１，日内相对标准偏差在３．３％以内，日间相对标准偏差在４％～１２％之间。本法操作简便、快速、专一性强、重现性好。     

高效液相色谱法测定肿瘤模型BALB/c裸鼠血浆中埃罗替尼的浓度及其药代动力学研究(英文)

本试验建立并验证了测定肿瘤模型BALB/c裸鼠血浆中表皮生长因子受体抑制剂埃罗替尼血药浓度的高效液相色谱方法。使用液液萃取的方法,用甲基叔丁醚与乙酸乙酯(9:1,v/v)的混合溶剂将血浆中埃罗替尼和内标3-(6,7-双(2-甲氧基乙基)喹唑啉-4-氨基)苯乙酮提取。使用Luna C_(18)(4.6 mm×250 mm,5μm)分析柱,流动相为乙腈-5 mM的KH_2PO_4缓冲盐(41:59,v/v),pH为5.2,紫外检测波长为345 nm,流速为1.0 mL/min。本方法在20-10 000 ng/mL的浓度范围内具有良好的线性关系,并且具有可接受的日内和日间精密度和准确度,精密度在1.69%-5.66%的范围内,准确度在105%-113%的范围内。埃罗替尼和内标的平均提取回收率分别为85.3%和96.1%。该方法成功地运用到肿瘤模型BALB/c裸鼠单剂量口服给药12.5 mg/kg埃罗替尼后的药代动力学研究,主要的药动学参数如下:C_(max)为4.67μg/mL,T_(max)为1.0 h,T_(1/2)为2.78 h,AUC_(0-24)h为18.0μg/mL·h。     

Quantitative determination of spinosin in rat plasma by liquid chromatography-tandem mass spectrometry method

A sensitive method for the quantitative determination of spinosin in rat plasma was developed and validated using high-performance liquid chromatographic separation with tandem mass spectrometric detection. The analytes of interest were extracted from rat plasma samples by methyl tert-butyl ether (MTBE) after acidification with 1.0% acetic acid aqueous solution. Chromatographic separation was achieved on an Agilent Zorbax SB-C(18) (50 mm x 4.6 mm, 5 microm) using a isocratic mobile phase consisting of acetonitrile-water (30:70, v/v) with 1% isopropyl alcohol and 0.01% heptafluorobutyric acid. The flow rate was 0.2 ml/min. The column temperature was maintained at 25 degrees C. Detection was performed on a triple quadrupole tandem mass spectrometer by selected reaction monitoring (SRM) mode via electrospray ionization (ESI). The calibration curve was linear over the range of 1.00-400 ng/ml in rat plasma, with 1.00 ng/ml of the lower limit of quantification (LLOQ). The inter- and intra-day precisions and accuracy for all samples were satisfactory. The validated method was successfully applied for the pharmacokinetic study of spinosin in rat. After oral administration of 20mg/kg spinosin to rats, the main pharmacokinetic parameters of T(max), C(max), T(0.5) and AUC(0-T) were 5.33+/-0.58 h, 132.2+/-10.6 ng/ml, 4.89+/-0.37 h, 1.02+/-0.09 microg h/l, respectively.     

高效液相色谱法测定人血浆中依诺沙星含量及药动学研究

目的建立测定人血浆中依诺沙星浓度的高效液相色谱方法。方法血浆样品经甲醇沉淀蛋白后,以乙腈∶0.05mol/L柠檬酸缓冲液(15∶85,pH 3.5)为流动相,经Hypersil-BDS C18(4.6mm×150mm,5μm)色谱柱分离,345nm波长检测。结果依诺沙星在0.05~5.0μg/ml浓度范围内线性关系良好,低、中、高三个浓度的提取回收率为44.8%~51.1%,日内、日间相对标准差为3.15%~6.61%。结论本方法准确、快速,可满足临床药动学研究的要求。