普罗帕酮对映体的高效液相色谱分析方法研究

目的:建立人体血浆中S 和R 普罗帕酮的高效液相色谱分析方法,为普罗帕酮对映体的临床药理学研究提供分析技术.方法:采用内标法和反相高效液相色谱法,以甲醇∶水∶冰乙酸:三乙胺(53∶47∶1.6∶0.5)为流动相,Shaudou Hypersil ODS柱为固定相,Li 1115为内标,流速为1.2 mL•min 1,在紫外检测波长250 nm处检测S 和R 普罗帕酮标准品和血浆中提取S 和R 普罗帕酮标准品的含量.结果:该方法的灵敏度AUF为0.01,最低检测限20 ng,标准曲线的线性范围为50～800 μg•L 1,S 和R 普罗帕酮的平均回收率分别为86.03%和84.17%,日内变异系数分别为8.2%和6.6%.结论:该法灵敏度高,重现性好,可用于普罗帕酮对映体的临床药理学研究.     

高效液相色谱法测定普罗帕酮血清浓度

高效液相色谱法测定普罗帕酮血清浓度（上海市第六人民医院临床药学研究室２００２３３）张毅普罗帕酮（Ｐｒｏｐａｆｅｎｏｎｅ）又名心律平，是一种抗心律失常药。对冠心病、高血压所引起的心律失常有较好的疗效［１］。但其服用剂量与血药浓度的关系，有强弱代谢之说［...     

反相高效液相色谱法同时测定人血浆中奎尼丁、利多卡因及普罗帕酮的浓度

目的 :建立反相高效液相色谱法同时测定人血浆中奎尼丁、利多卡因及普罗帕酮的浓度。方法 :应用UltrasphereC18柱(4.6mm× 2 5 0mm) ,流动相为甲醇 水 冰醋酸 三乙胺 (6 2 .3∶37.7∶0 .0 34∶0 .0 6 8) ,pH 6 .0 2 ,紫外 2 2 0nm检测。结果 :奎尼丁、利多卡因、普罗帕酮平均回收率分别为 97.3% ,98.9% ,99.0 % ,日内日间精密度分别为 (2 .11～ 6 .0 1) % ,(1.2 5～ 4.35 ) % ,(1.5 0～ 4.2 7) %。结论 :方法简单、灵敏、准确 ,可用于临床治疗药物监测。     

高效液相色谱法测定普罗帕酮血浆浓度

本文建立了高效液相色谱法测定人体内普罗帕酮血浆浓度。以YWG-C_(18)(10μm)为固定相,改性甲醇-乙腈-醋酸盐缓冲液(45.5:19.5:35)为流动相,用达克罗宁作内标在254nm波长处定量测定。方法最低检测限为5ng(S/W=3),血浆中最低检测浓度为25ng/ml,普罗帕酮血浆浓度在50～500ng/ml范围内线性关系良好,方法回收率为100.5％,不同浓度水平测定蛄果的日内和日间变异系数均小于3％。方法重现性好,专一性强,内源性物质不干扰,操作简便,快速,能适合梏床血药浓度监测及药代动力学研究。     

高效液相色谱法测定老年患者普罗帕酮血清浓度

作者建立改良的测定人血清中普罗帕酮反相ＨＰＬＣ法，固定相为ＬｉｃｈｒｏｓｏｒｂＲＰ－１８，流动相为甲醇：醋酸钠缓冲液：二乙胺（７４．５：２５：０．５ｖ／ｖ），流速为１ｍ１／ｍｉｎ，以安定为内标，紫外检测限为５ｎｇ，血浆中最低检测浓度４０ｎｇ／ｍｌ，在５０－３２００ｎｇ／ｍｌ浓度范围内线性良好，相关系数ｒ＝０．９９９８。用本方法测定１６名老年心律失常患者口服不同剂量普罗帕酮血浓，对老年患者服用普罗帕     

普罗帕酮两对映体间的药动学和药效学相互作用研究

采用随机、交叉、双盲法给予8名健康受试者多次剂量（150mg,q6h)来考察普罗帕酮三种片剂（消旋体、左旋体、右旋体）和安慰剂,立体选择性高效液相色谱法测定稳态时一个给药间隔（0－6h)的血浆中两对映体浓度,心电图同时记录PR、QRS和QTc间隙并测试最大运动心率HRmax及血压变化情况,TopFit软件拟合参数。结果表明,三种制剂的平均驻留时间MRT及峰时Tmax无差别。给予消旋体片剂后,右旋体的清除率C1明显低于左旋体（P＜0.05),单纯给予对映体时,右旋体的清除率则大于左旋体（P＜0.001)。左旋体的存在提高了右旋体的血浆浓度,增强了β-受体阻断作用。普罗帕酮在人体内消除存在立体选择性,且两对映体产生了药效学上的相互作用。临床应用消旋体可不作剂量调整,但对某些患者应慎重使用。     

普罗帕酮对映体的人体药物动力学

目的:研究普罗帕酮(PPF)对映体人体药物动力学差异.方法:8名健康受试者po盐酸PPF消旋片150mg,q6 h,4 d.RP-HPLC法测定血药浓度,采用TopFit软件,以非室模型计算药物动力学参数并比较.结果:(S)-PPF与(R)-PPF的(?)分别为(219±111)、(147.75±80.25)ng/ml;Cl值分别为(1226±7510)、(1678±625)ml/min;S/R-AUC比为 1.49±0.34.结论:PPF对映体存在明显的人体药物动力学立体选择性差异.     

高效液相色谱法测定血浆中氯胺酮对映体的浓度

目的:建立以高效液相色谱手性固定相法测定血浆中氯胺酮对映体浓度的方法。方法:色谱柱为Chirobiotic V手性柱,流动相为甲醇-冰醋酸-三乙胺(100∶0.02∶0.02),检测波长为269nm,流速为1mL·min-1,内标为非那西丁。结果:S-氯胺酮、R-氯胺酮分别在19.5～2600(r=0.9992)、26～2600ng·mL-1(r=0.9989)范围内线性关系良好,最低检测浓度分别为13.0、19.5ng·mL-1;相对回收率分别为99.48%～103.40%、98.53%～103.20%,绝对回收率分别为63.2%～73.1%、64.5%～72.3%;日内RSD分别为3.3%～6.4%、3.5%～5.7%,日间RSD分别为7.1%～9.7%、6.3%～9.9%。结论:本方法简便、准确、灵敏、快速、专属,可用于血浆中R-氯胺酮和S-氯胺酮的测定及药动学研究。     

高效液相色谱法测定奎尼丁血药浓度

本文介绍了用高效液相测定奎尼丁(Quinidine)血药浓度,以辛可宁(Cinchon-ine)为外标,水:乙腈(91:9v/v)为流动相。奎尼丁出峰时间6.6min,辛可宁出峰时间3.8min,检测最低浓度0.1μg/ml,线性范围为1～16μg/ml。     

Determination of Codeine in Plasma by High-Performance Liquid Chromatography

An automated, sensitive, and selective reverse-phase high-performance liquid chromatographic assay has been developed to measure codeine in plasma. The analysis requires only 1 ml plasma and is accomplished by detection of the fluorescence of codeine following extraction and concentration. The method is simple and rapid, involving a one-step extraction of codeine from alkalinized (pH 10.0) plasma into an organic layer of hexane/dichloromethane, 2/1. The organic layer was evaporated under nitrogen and the residue reconstituted with the mobile phase. The samples were chromatographed on a reverse-phase C-18 column using a mobile phase of acetonitrile–phosphate buffer, 80/20 (pH 5.80). The codeine and internal standard, N-allylnorcodeine, peaks were detected using a fluorescence detector. The retention times were 8.6 min for the internal standard and 11.3 min for codeine. Standard curves were linear from 10 to 250 ng/ml. The assay was validated by direct comparison with a gas chromatographic procedure that employed nitrogen–phosphorus detection. The assay has been employed for the analysis of several codeine studies using human, dog, and rat plasma.     

The Stereospecific Determination of Fluoxetine and Norfluoxetine Enantiomers in Human Plasma by High-Pressure Liquid Chromatography (HPLC) with Fluorescence Detection

A quantitative method for the simultaneous HPLC resolution and detection of the enantiomers of (R,S) fluoxetine (F) and their metabolites (R,S) norfluoxetine (N) in human plasma has been developed. F is a serotonin uptake inhibitor used in the treatment of depression and is administered as a racemate. After liquid–liquid extraction and derivatization with (R) napthyl ethyl isocyanate (NEI), the separation and detection of the resultant diasteriomers were achieved using normal phase HPLC and fluorescence. The four NEI diastereomers and the internal standard [(–)-N-methyl--(2-methylphenoxy) benzenepropanamine hydrochloride], representing the enantiomers S-F, R-F, S-N, and R-N were resolved within 15 min. The assay for each analyte was linear using two concentration ranges of 1–10 and 10–500 ng/ml of human plasma. The precision and accuracy are reported as the coefficient of variation (%CV) and relative error (%RE). The sum of the chiral HPLC results from plasma samples were compared to the achiral gas chromatographic/electron capture (GC/EC) results. The correlation between these two methods, for total F and N, resulted in r ² values of 0.98 and 0.89, respectively. The chiral HPLC method is currently being applied to clinical studies for the evaluation of the enantiomeric disposition of F.     

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。     

Determination of a Novel Antiarrhythmic Agent ACC-9358 in Human Plasma by High-Performance Liquid Chromatography

A liquid chromatographic method for the determination of ACC-9358, an antiarrhythmic agent, in human plasma is described. ACC-9358 was extracted from plasma into chloroform and back extracted into 0.01 N hydrochloric acid. ACC-9358 in the acidic extract was eluted from a Novapak C18 column using a 87:13:0.1 (by volume) mixture of phosphate buffer (pH 3.0), acetonitrile, and triethylamine as the mobile phase and measured at 280 nm. The average extraction recoveries were 78.4 and 85.4% at the 0.5- and 5-µg/ml level, respectively. Standard curves were linear and reproducible over the concentration range of 0.01–10 µg/ml, with coefficients of determination better than 0.999. Coefficients of variation for both within-day and day-to-day analysis were less than 11%. The assay method is sensitive, reproducible, and suitable for disposition studies of ACC-9358 in humans.     

HPLC法测定人血浆中舒芬太尼的浓度

目的:建立测定人血浆中舒芬太尼浓度的高效液相色谱法。方法:血浆样品经正己烷-乙醇（95:5,）提取后,以乙腈-5 mmol·L^-1磷酸二氢钾缓冲液（40:60,pH 6.1）为流动相,流速1.0 ml·min^-1,色谱柱为Agilent Extend C₁₈（150 mm×4.6 mm,5μm）,柱温25℃,检测波长230 nm。结果:血浆内源性杂质不干扰待测物测定,舒芬太尼的线性范围为2.014～201.400 g·L^-1,定量下限为2.014 g·L^-1,日内、日间RSD均小于6%。样品3次冻融及在提取后,4℃下12 h内稳定性良好。结论:该法灵敏、快速、准确,操作简便,可用于舒芬太尼的血药浓度监测和临床药动学研究。     

RP-HPLC法测定人血浆中头孢吡肟的含量

目的建立RP—HPI．c法测定人血浆巾头孢吡肟的浓度。方法色谱柱：NueleodurC18分析柱（4．6mm×250mm,5μm）,流动相：0.03％三氟乙酸缓冲液／乙腈（81／19,V／V,冰醋酸调节pH=5）,流速1．0ml／min,检测波长270nm,柱温30℃,进样量20μl。结果头孢吡肟线性范围为0．02～5．0μg／ml。头孢吡肟的最低检测限为0．02μg／ml,日内、日间RSD均小于5％,相对回收率为97．6％～104．5％,提取回收率均大于91．3％。结论该方法灵敏、简便、准确度高,可用于头孢吡肟的血药浓度测定。     

高效液相荧光色谱法测定人血浆中唑吡坦的浓度

目的：建立测定人血浆中唑吡坦浓度的高效液相荧光色谱法。方法：血浆样品经甲醇沉淀后,以甲醇-1％醋酸液（40：60）为流动相,流速为0．3ml·min^-1,色谱柱为Agilent Zorbax C18（150mm×3mm,3．5μm）,柱温为22℃,荧光检测波长：激发波长（λex）254nm,发射波长（λem）390nm。结果：血浆内源性杂质不干扰待测物测定,唑吡坦的线性范围为2～300μg·L^-1,定量下限为2μg·L^-1,日内、日间RSD均〈5％。样品经3次冻融及再沉淀后,4℃下6h内稳定性良好。结论：该法灵敏、快速、准确,操作简便,线性范围宽,可用于唑吡坦的临床药动学研究。