反相HPLC法测定兔血浆异钩藤碱浓度及其药物代谢动力学

用ODS柱分离,甲醇—水(95∶5)为流动相,检测波长UV254nm,建立了兔血浆异钩藤碱浓度的HPLC测定方法。结果显示,血药浓度在0016～16μg·ml^-1范围内呈线性关系,血浆最低检测浓度为0.016μg·ml^-1,绝对回收率为80.5%～85.1%。兔iv IRHY 2及5mg·kg^-1,药代动力学过程符合二室开放模型,T_1/2β分别为1.32h和1.25h。兔经十二指肠给2及5mg·kg^-1后,T_1/2β分别为1.75h和1.26h。生物利用度为42.4%～69.4%。此法简便、快速。IRHY在兔体内吸收迅速,消除也较快。     

高效液相色谱法测定人血清和尿中盐酸青藤碱浓度及药代动力学研究

用RP-HPLC法,以三唑仑为内标,反相C₁₈为分析柱,乙腈—0.01mol·L^-1磷酸二氢钠—四甲基乙二胺(46∶54∶0.22v/v)为流动相,磷酸调至pH6.9,检测波长263nm,测定血清和尿中盐酸青藤碱浓度,线性范围分别为6～480ng·mL^-1和0.06～3μg·mL^-1,平均回收率75.88%和91.35%,日内日间误差小于5%,最低检测浓度血清4ng·mL^-1,尿40ng·mL^-1。8名健康男性志愿者单次口服盐酸青藤碱片80mg,测定血清及尿浓度,该药符合二室开放模型,体内消除符合一级动力学消除过程,主要药代动力学参数:T_1/2α0.791±0.491h,T_1/2β9.397±2.425h,T_{max 1.040±0.274h,Cmax246.604±71.165ng·mL^-1,AUC 2651.158±1039.050ng·h·mL^-1,CL 0.033±0.01ng·mL^-1。}     

小鼠血浆中马钱素的高效液相色谱测定法及药代动力学

目的建立测定小鼠血浆中马钱素浓度的高效液相色谱法,并研究马钱素在小鼠体内的药代动力学。方法色谱柱为C18柱,流动相甲醇-水(30∶70),流速为0.8 mL·min^-1,检测波长240 nm;血浆样品用固相萃取法预处理。结果线性范围0.01～5.00 μg·mL^-1。日内RSD<10%,日间RSD<15%,回收率86.0%～91.5%,最低定量浓度为10 ng·mL^-1。ig给药0.5 h后血浆药物浓度达峰值,C_max为6.8 μg·mL^-1,_t1/2α为26.1 min,_t1/2β为29.01 min。结论 该方法灵敏度高,操作方便,适用于马钱素的药代动力学研究;本品口服吸收快消除也快。     

何首乌有效成分二苯乙烯苷的药代动力学研究

目的建立小鼠和兔血浆中二苯乙烯苷浓度的HPLC测定方法,研究何首乌中二苯乙烯苷在小鼠和兔体内的药代动力学行为。方法用Diamonsil^TM C₁₈色谱柱(250 mm×4.6 mm,5 μm),以乙腈-甲醇-1%甲酸(15∶18∶67)为流动相,流速1.0 mL·min^-1,检测波长320 nm。结果线性范围为0.41～42.0 μg·mL^-1(γ=0.9999),最低检测浓度为0.051 μg·mL^-1。高、中、低3种不同浓度的平均回收率分别为97.98%,101.7%和104.5%,日内精密度RSD分别为8.7%,2.9%和5.5%。小鼠和兔iv二苯乙烯苷后药代动力学行为均符合二室模型,药代动力学参数分别为:T_1/2α=1.9,2.7 min;T_1/2β=8.3,13.5 min;K₂₁=6.6,4.2 h^-1;K₁₂=3.8,3.0 h^-1;K₁₀=16.0,11.2 h^-1;V_c=0.090,0.198 L·kg^-1;AUC=6.918,4.530 mg·h·L^-1;CL=1.445,2.208 L·h^-1·kg^-1。小鼠ig给药后二苯乙烯苷在胃肠道内的吸收不规则,且血药浓度很低,药代动力学行为不符合房室模型。结论建立了二苯乙烯苷血药浓度的HPLC测定方法,阐明了二苯乙烯苷的药代动力学特征。方法的专属性高,操作简便,结果准确。     

微渗析结合RP-HPLC研究盐酸平阳霉素在家兔血中的药代动力学

采用微渗析技术研究盐酸平阳霉素在体药代动力学，用Supelco RP-amide C₁₆柱进行样品的HPLC分析，盐酸平阳霉素的血药浓度用3P87程序处理。结果表明，家兔静注盐酸平阳霉素后，渗析液中的药物浓度在1.04～66.56 μg·mL^-1时，浓度与峰面积有良好的线性关系(R²=0.999 4)。微渗析探针的在体回收率为(42.8±3.4)%(n =6)。所测血药浓度经3P87程序拟合后，药-时曲线符合二室模型，T_1/2α及T_1/2β分别为14.9及60.3 min。因此，该方法可用于盐酸平阳霉素药代动力学研究。     

HPLC/MS法研究左旋黄皮酰胺及其代谢物在Beagle犬血浆中的药代动力学HPLC/MS法研究左旋黄皮酰胺及其代谢物在Beagle犬血浆中的药代动力学

目的用HPLC/MS法研究左旋黄皮酰胺［(-)-clau］及其代谢物6-羟基-黄皮酰胺(6-OH-clau)在Beagle犬血浆中的药代动力学过程。方法Beagle犬灌胃左旋黄皮酰胺30 mg·kg^-1，采集静脉血样，血浆经乙酸乙酯萃取分离后，用HPLC/MS选择性正离子检测内标(格列吡嗪，［M+H］⁺，m/z 446)法测定左旋黄皮酰胺(［M+H］⁺，m/z 298)及6-羟基-黄皮酰胺(［M+H-H₂O］⁺，m/z 296)的浓度，以甲醇-水-冰醋酸(60∶40∶0.8)为流动相，流速1.0 mL·min^-1。用3P97软件计算药代动力学参数。结果左旋黄皮酰胺和6-羟基-黄皮酰胺分别在1.0～200 ng·mL^-1和0.2～40.0 ng·mL^-1线性关系良好(r>0.999)，萃取回收率均大于85%。原药及其代谢物的体内过程均符合二室模型；左旋黄皮酰胺及6-羟基-黄皮酰胺的C_max分别为(21±10) ng·mL^-1和(3.9±2.2) ng·mL^-1；T_max分别为(0.8±0.5) h和(1.3±0.5) h；T_1/2α分别为(0.9±0.6) h和(1.4±0.6) h；T_1/2β分别为(19±23) h和(13±12) h；AUC_{0-24 h}分别为(69±14) h·ng·mL^-1和(12±7) h·ng·mL^-1。结论Beagle犬灌胃左旋黄皮酰胺后迅速吸收，血药浓度一相消除很快，但末端消除较慢；其代谢物6-羟基-黄皮酰胺血药浓度经时过程与左旋黄皮酰胺相似，但血药浓度相对较小。     

血浆中葛根素的高效液相色谱测定法及其在狗体内的药代动力学

为阐明葛根素的代谢规律,建立了血浆中葛根素的高效液相色谱荧光检测法。用YWG-C₁₆为固定相,甲醇—水—0.1mol·L^-1磷酸缓冲液(pH7.4)(450∶522.5∶27.5)为流动相,大豆甙元作内标,以峰高比计算含量。葛根素的平均回收率为95.3%,RSD为4.8%;最低检测量为0.04ng,相当于10ng·mL^-1血浆。方法灵敏、特异、简便、快速。狗静注2.25mg·kg^-1葛根素的血药浓度—时间曲线符合开放二室模型,T_1/2α及T_1/2β分别为6.0及57.4min。     

救必应酸在大鼠体内的口服生物利用度研究

摘 要 目的：研究救必应酸在大鼠体内药动学和口服生物利用度。方法: 建立测定大鼠血浆中救必应酸浓度的RP HPLC法。考察大鼠经灌胃和尾静脉给予40 mg·kg^-1的救必应酸后血药浓度变化。采用3p97软件计算分析药动学参数和口服生物利用度。结果: 灌胃组大鼠的C_max为（0.81±0.22）μg·mL^-1,T_max为（45.24±5.13） min,T_1/2为（101.47±8.25） min,AUC为（76.3±13.68）μg·min^-1·mL^-1;静脉注射组的T_1/2为（73.68±11.02） min,AUC为（1 687.4±29.54）μg·min^-1·mL^-1。救必应酸口服利用度为4.52%。结论:救必应酸的口服生物利用度较差。     

家犬单剂量和多剂量口服阿昔莫司缓释制剂的药代动力学和生物等效性研究

目的研究阿昔莫司缓释片在家犬体内单剂量和多剂量的药代动力学和生物等效性。方法测定6只家犬单剂量和多剂量口服缓释片和普通胶囊后的血药浓度。结果阿昔莫司的药-时曲线符合非隔室模型。单剂量给药后，缓释片和普通胶囊的AUC分别为(158±30)和(147±37) μg·h·mL^-1；T_max分别为(4.3±0.8)和(2.6±1.3) h；C_max分别为(29±6)和(42±10) μg·mL^-1；T_1/2分别为(2.3±0.7)和(1.60±0.10) h；MRT分别为(6.0±0.8)和(3.9±0.7) h；F_r为(108±16)%。多剂量给药后，缓释片和普通胶囊的AUC分别为(209±23)和(195±26) μg·h·mL^-1；T_max分别为(6.3±0.8)和(3.4±1.5) h；C_max分别为(27±4)和(36±5) μg·mL^-1；Cmin分别为(2.2±1.0)和(0.20±0.20) μg·mL^-1；C_av分别为(8.7±1.0)和(8.1±1.1) μg·mL^-1；FI分别为(293±73)%和(448±91)%；F_r为(114±19)%。结论单剂量实验的双单侧检验结果表明：缓释片和普通胶囊生物等效；缓释片具有良好的缓释效果。多剂量实验结果表明：缓释片和普通胶囊生物等效；缓释片的波动系数优于普通胶囊。     

大鼠血浆中马来酸曲美布汀的HPCE测定法及药物动力学

目的　建立快速、准确测定大鼠血浆中马来酸曲美布汀浓度的HPCE方法,并用于其在大鼠体内的药物动力学研究。方法　以盐酸麻黄碱为内标,0.03mol·L^-1磷酸二氢钠(pH6.0)为运行缓冲溶液,紫外检测波长为214nm。血浆样品经乙腈除蛋白后,于50℃水浴用氮气吹干,残渣溶于甲醇-水(1:1),进样分析。结果　线性范围5-200μg·L^-1,日内RSD<14%,日间RSD<13%,回收率为72.8%-87.9%,最低定量浓度为5μg·L^-1。ig给药30min后,血浆中药物浓度达峰值,T_1/2(Ke)为173min,Ke为5.6×10^-3min^-1,AUC为7.83μg·min·mL^-1。结论　方法灵敏度高,操作简便,适用于马来酸曲美布汀的药物动力学研究。     

Metabolism of aceclofenac to diclofenac in the domestic water buffalo Bubalus bubalis confirms it as a threat to Critically Endangered Gyps vultures in South Asia

Vulture declines in South Asia were caused by accidental poisoning by the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Although veterinary use of diclofenac has been banned, other vulture-toxic NSAIDs are legally available, including aceclofenac, which has been shown to metabolise into diclofenac in domestic cattle. We gave nine domestic water buffalo the recommended dose of aceclofenac (2 mg kg⁻¹ body weight), collected blood at intervals up to 48 h, and carried out a pharmacokinetic analysis of aceclofenac and its metabolite diclofenac in plasma. Aceclofenac was rapidly converted to diclofenac, and was barely detectable in plasma at any sampling time. Diclofenac was present within 20 min, and peaked 4–8 h after dosing. Aceclofenac is a prodrug of diclofenac, and behaves similarly in domestic water buffalo as it did in domestic cattle, posing the same risk to vultures. We recommend an immediate ban on the veterinary use of aceclofenac across vulture-range countries.     

Metronidazole excretion in human milk and its effect on the suckling neonate.

1. Milk and plasma metronidazole and hydroxymetronidazole concentrations were measured in 12 breast-feeding patients following multiple doses of metronidazole (400 mg three times daily). All patients received metronidazole in combination with other broad spectrum antibiotics. 2. Plasma concentrations of both parent drug and metabolite were measured in seven suckling infants. Thirty-five infants were monitored for adverse reactions to maternal metronidazole therapy and two further groups of suckling infants, those whose mothers received either ampicillin alone or no drug therapy, were recruited as controls. 3. The mean milk to plasma ratio (M/P) was 0.9 for metronidazole and 0.76 for hydroxymetronidazole while the mean milk metronidazole concentrations (around Cmax) were 15.5 micrograms ml-1. The mean milk hydroxymetronidazole concentration was 5.7 micrograms ml-1. 4. Infant plasma metronidazole concentrations ranged from 1.27 micrograms ml-1 to 2.41 micrograms ml-1, and the corresponding hydroxymetronidazole concentrations from 1.1 to 2.4 micrograms ml-1. 5. There were no significant increases in adverse effects in infants which could be attributable to maternal metronidazole therapy. 6. Metronidazole was excreted in milk at concentrations which caused no serious reactions in the infants studied. The drug may therefore be administered at doses of 400 mg three times daily to mothers wishing to breast-feed their infants.     

Pharmacokinetics of triflusal and its main metabolite in rats and dogs.

The methods for determining plasma concentrations of triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) that have been described, do not distinguish between the drug and its main metabolite HTB (2-hydroxy-4-trifluoromethyl benzoic acid). In the present study, we have developed a new analytical technique based on HPLC that enabled us to carry out a pharmacokinetic study of the drug and its metabolite in animals. An intravenous or oral dose of 50 mg/kg was administered to male Sprague-Dawley rats, and 15 mg/kg was administered to beagle dogs. Plasma levels of triflusal and HTB were determined. In rats, triflusal was quickly eliminated from plasma with a biological half-life (t1/2) of 2.7 min and a clearance (Cl) of 73.4 (ml/kg)/min. The elimination of HTB was much slower with a t1/2 of 21.5 h and a Cl of 5.1 (mg/kg)/h. The maximum concentration (Cmax) of triflusal in rats after an oral administration was 8.1 +/- 2.0 micrograms/ml reached between 2.5 and 10 min. The Cmax of HTB was 237.7 micrograms/ml and was achieved at 0.7 h. The bioavailability of triflusal in rats was only 10.6% while the bioavailability of HTB was more than 100% indicating an important first pass effect. In dogs the t1/2 of triflusal was 14.4 +/- 5.9 min and the Cl was 25.1 +/- 4.7 (ml/kg)/min. HTB was also eliminated very slowly with a t1/2 of 71.1 +/- 12.5 h and a Cl of 2.4 +/- 0.3 (ml/kg)/h. The Cmax of triflusal in dogs was 13.3 +/- 2.9 micrograms/ml and was reached after 19.2 +/- 6.1 min (tmax).(ABSTRACT TRUNCATED AT 250 WORDS)     

青蒿琥酯在奶牛体内的药代动力学与代谢

青蒿琥酯(artesunate,AS)是抗疟新药青蒿素的一个活性衍生物。近年来我国兽医工作者将其用于治疗牛羊泰勒氏焦虫病及双芽、巴贝斯焦虫病、鸡球虫病和耕牛血吸虫病,也收到了满意的效果。AS在大白鼠、兔、狗及人体内的药代动力学研究已见报道。本     

Single dose disposition of chloroquine in kwashiorkor and normal children--evidence for decreased absorption in kwashiorkor.

The single dose disposition of chloroquine was studied in five children with kwashiorkor and six normal control children after an oral dose of 10 mg kg-1 of chloroquine base. Plasma concentrations of chloroquine and its main metabolite were assayed by high performance liquid chromatography (h.p.l.c.). Chloroquine was detectable for up to 21 days in all the subjects. Chloroquine was detectable in all the subjects within 30 min after giving the drug except in one subject. Peak levels were reached between 0.5 and 8 h in all the subjects (with no significant difference in the tmax between the two groups of children). Peak plasma chloroquine concentrations in the children with kwashiorkor varied from 9 ng ml-1 to 95 ng ml-1 (mean 40 +/- 34 ng ml-1). Peak chloroquine concentrations in the controls varied between 69 ng ml-1 and 330 ng ml-1 (mean 134 +/- 99 ng ml-1). The mean AUC in the kwashiorkor children was significantly lower than the mean AUC in the control children (P less than 0.001). Peak plasma desethylchloroquine concentrations in the children with kwashiorkor varied between 3 and 13 ng ml-1 (mean 6 +/- 9 ng ml-1) while in the controls the concentrations varied between 14 and 170 ng ml-1 (mean 50 +/- 61 ng ml-1). There was no significant difference in the half-life of chloroquine between the kwashiorkor children and the normal control children. The possible influence of a different binding and distribution pattern of chloroquine in kwashiorkor could not be assessed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学谭力周继红罗楠袁倚盛（南京军区南京总医院中心仪器分析科，南京２１０００１）阿莫西林（ａｍｏｘｉｃｉｌｉｎ）为β内酰胺类抗生素，其抗菌谱广，口服受食物影响小，对大多数病人耐受性良好，因而在临床上得以广泛...     

Novel assay and pharmacokinetics of levamisole and p-hydroxylevamisole in human plasma and urine

A new gas chromatographic method was developed for the quantification of levamisole in human plasma and urine, using a nitrogen-phosphorus flame ionization detector. The adsorption of the drug onto glass was prevented by treating the glassware with a siliconizing agent. The sensitivity of the assay was 10 ng ml-1 and as low as 2 ng ml-1 can be detected in plasma. The urinary metabolite p-hydroxylevamisole was analysed by high performance liquid chromatography with ultraviolet detection. The sensitivity of this assay was 0.50 micrograms ml-1. Plasma and urinary concentrations of levamisole were determined in 10 healthy volunteers including seven men and three women following the administration of a single 150 mg dose of levamisole. Levamisole was rapidly absorbed (tmax 1.5 h), giving a peak plasma concentration of 716.7 +/- 217.5 ng ml-1. The plasma elimination half-life of levamisole was 5.6 +/- 2.5 h. Only 3.2 +/- 2.9 per cent of the oral dose was recovered as unchanged drug in the urine, suggesting the importance of clearance of levamisole by routes other than the kidney, and most probably by hepatic metabolism. The urinary concentrations of p-hydroxylevamisole were determined before and after hydrolysis of the urine samples with beta-glucuronidase, and the level of conjugation of the metabolite with glucuronic acid was then estimated. Cumulative recovery of the metabolite accounted for 1.6 +/- 1.1 per cent and 12.4 +/- 5.5 per cent of the oral dose of levamisole before and after hydrolysis, respectively, indicating that p-hydroxylation is a relatively important route of metabolism of levamisole, and that the p-hydroxylated metabolite is excreted mainly in conjugation with glucuronic acid. Except for the absorption rate of levamisole which is approximately twice as rapid in women as in men, there is no marked difference in the pharmacokinetics of levamisole between healthy men and women.     

Pharmacokinetics of artemether after oral administration to healthy Thai males and patients with acute, uncomplicated falciparum malaria.

1. The pharmacokinetics of artemether were investigated (a) in six healthy male Thai volunteers after single 200 mg oral doses and (b) in eight male Thai patients with acute uncomplicated falciparum malaria after an initial 200 mg oral dose followed by 100 mg at 12 h then 100 mg daily for 4 days. 2. In the healthy subjects, median (range) maximum plasma concentrations of artemether of 118 (112-127) ng ml-1 were reached at 3 (1-10) h. Thereafter, drug concentrations declined monoexponentially with a median (range) t1/2.z of 3.1 (1.0-9.6) h. The median (range) AUC and MRT values were 1.10 (0.33-4.44) micrograms ml-1 h and 8.3 (3.5-20.8) h. The median Cmax value of dihydroartemisinin, an active metabolite, was 379 (162-702) mg ml-1 at 6 (2-12) h. Its median AUC value was 6.6 (0.83-38.7) micrograms ml-1 h; the apparent t1/2.z was 10.6 (4.7-19.2) h and the median MRT value was 16.0 (5.0-41.0) h. 3. In the patients, a higher Cmax value of parent drug than those observed in healthy subjects (median and range of 231 (116-411) ng ml-1), was reached at 3 (1-3) h after the first dose. Steady state was reached after the third dose (24 h) and concentrations fluctuated over the range of 36-60 ng ml-1. The respective median (range) values of AUC and t1/2.z were 5.8 (3.76-12.9) micrograms ml-1 h and 4.2 (2.5-5.3) h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simultaneous determination of aceclofenac and its three metabolites in plasma using liquid chromatography-tandem mass spectrometry

A new LC/MS/MS-based method allows simultaneous determination of aceclofenac and its three metabolites (4'-OH-aceclofenac, diclofenac, and 4'-OH-diclofenac) in plasma. After acetonitrile-induced precipitation of proteins from the plasma samples, aceclofenac, 4'-OH-aceclofenac, diclofenac, 4'-OH-diclofenac, and flufenamic acid (an internal standard) were chromatographed on a reverse-phase C(18) analytical column. The isocratic mobile phase of acetonitrile/0.1% formic acid((aq)) [80:20 (v/v)] was eluted at 0.2 mL/min. Quantification was performed on a triple-quadrupole mass spectrometer employing electrospray ionization, and the ion transitions were monitored in multiple reaction-monitoring mode. The monitored transitions for aceclofenac, diclofenac, 4'-OH-diclofenac, 4'-OH-aceclofenac and flufenamic acid were m/z 352.9-->74.9, 296.1-->251.7, 311.8-->267.7, 368.9-->74.9, and 279.9-->235.9, respectively. The coefficient of variation of the assay precision was less than 6.5%, and the accuracy ranged from 93% to 103%. The limits of detection were 2 ng/mL for aceclofenac and 0.2 ng/mL for both diclofenac and 4'-OH-diclofenac. This method was used successfully to measure the concentrations of aceclofenac and its three metabolites in plasma from healthy subjects after administration of a single 100-mg oral dose of aceclofenac. This analytic method is a very simple, sensitive, and accurate way to determine the pharmacokinetics of aceclofenac and its metabolites.     

氯唑沙宗及其代谢物的HPLC测定方法和药代动力学研究

目的旨在建立氯唑沙宗及其代谢物的方法。应用高效液相色谱法,内标物为5-fluorobenzoxazolone,经乙酸乙酯提取,紫外检测波长为287nm。结果表明,6-羟氯唑沙宗、内标物及氯唑沙宗的保留时间分别为6.12,10.47和18.65min。6-羟氯唑沙宗及氯唑沙宗在0.5～20μg·ml^-1血浆浓度范围内线性关系良好,回收率均在82.80%～100.76%之间,当日及日间相对标准差分别小于8%和11%。两药的最低检测浓度分别为0.2和0.5μg·ml^-1。多种常用药物对样品的色谱峰无干扰。曾对8名健康受试者单次口服氯唑沙宗400mg的药代动力学进行了观察。提示此方法可用于氯唑沙宗的体内氧化代谢研究。