联苯双酯的吸收、分布、代谢和排泄

用高效液相层析和放射性同位素法研究了联苯双酯在大、小鼠体内的代谢及人的排泄。联苯双酯口服后吸收缓慢而不完全;静脉给药后t1/2β为5.78小时,分布容积较大,且易向脂肪组织转移。动物和人经口给药后,原形药物的70%左右自粪排出。自尿和胆汁排出者均为其代谢产物。体外温孵证明,联苯双酯可被肝脏迅速代谢。灌胃给药后用HPLC法很难测到血浆和组织中的药物,提示药物吸收后被迅速转化,可能存在明显的首过作用。     

联苯双酯的吸收、分布、代谢和排泄

用高效液相层析和放射性同位素法研究了联苯双酯在大、小鼠体内的代谢及人的排泄。联苯双酯口服后吸收缓慢而不完全;静脉给药后t1/2β为5.78小时,分布容积较大,且易向脂肪组织转移。动物和人经口给药后,原形药物的70％左右自粪排出。自尿和胆汁排出者均为其代谢产物。体外温孵证明,联苯双酯可被肝脏迅速代谢。灌胃给药后用HPLC法很难测到血浆和组织中的药物,提示药物吸收后被迅速转化,可能存在明显的首过作用。     

用~2H-标记物和GC-MS分离鉴定联苯双酯在大鼠尿中的一个代谢产物

联苯双酯(BDD)是人工合成的五味子丙素类似物,其化学结构为4,4′-二甲氧基-5,6,5′,6′-二次甲二氧基-2.2′-二甲氧羰基联苯,已用于迁、慢性肝炎的治疗。临床证明,该药降血清谷丙转氨酶的作用很强。为阐明其在体内的转化过程,并进一步研究其构效关系,我所曾用放射性同位素结合薄层层析对联苯双酯的代谢途径进行过研究,并分     

双苯氟嗪在大鼠体内的代谢途径

目的研究双苯氟嗪在大鼠体内的代谢途径。方法大鼠ig双苯氟嗪，LC/DAD/MS法分离、鉴定尿中代谢产物。结果在大鼠尿中有1-(4-氟苯基)-4-哌嗪基丁酮及其葡糖醛酸结合物、4-羟基二苯甲酮及其葡糖醛酸结合物、4-氟-γ-羟基苯丁酸及其葡糖醛酸和硫酸结合物、二苯甲醇及其葡糖醛酸结合物和双苯氟嗪，二苯甲酮。结论 双苯氟嗪在大鼠体内主要经哌嗪环1-和4-氮脱烷基代谢，部分代谢物再与葡糖醛酸和/或硫酸结合。     

高效液相-质谱联用法对盐酸关附甲素在大鼠尿中代谢物的研究

目的研究盐酸关附甲素在大鼠尿中的代谢产物。方法大鼠iv盐酸关附甲素后收集尿,用高效液相-质谱联用方法测定。通过与标准化合物的色谱保留时间、分子离子峰、碎片离子峰对照从而鉴定I相代谢物。通过用葡糖醛酸酶和硫酸酯酶酶解鉴定其水解产物(苷元)从而确定II相结合物。结果大鼠尿中发现I相代谢物关附醇胺和关附壬素;尿经过葡糖醛酸酶和硫酸酯酶酶解后,产生关附甲素和关附壬素。结论盐酸关附甲素在大鼠体内可以转化为关附壬素、关附醇胺、关附甲素葡糖醛酸和硫酸结合物、关附壬素葡糖醛酸和硫酸结合物。经过生物转化,代谢产物的极性增加,药效下降。     

用2H-标记物和GC-MS分离鉴定联苯双酯在大鼠尿中的一个代谢产物

Dimethyl-4, 4′-dimethoxy-5, 6, 5′, 6′-dimethylenedioxybiphenyl-2, 2′-dicarboxylate (biphenyldimethyldicarboxylate; BDD), a synthetic compound, has been used in the treatment of chronic hepatitis with good results in reducing s-GPT. Previous work in our laboratory studied its metabolites using ³H-labeled compound in combination with TLC and found that its main methabolic pathway is demethylation followed by conjugation with glucuronic acid. This paper reports the isolation and identification of a metabolite of BDD from rat urine using ²H-labeled compound and GC-MS. Rats fasted for 12h were intragastrically given a mixture of ²H-labeled (consisting of monodeutero-and dideutero-BDD in the ratio about 1:1.3)and non-labeled BDD 150mg/kg and placed in metabolism cages for urine collection. The 24h urine was filtered and extracted three times each with 5ml of methylenedichloride. The extracts were pooled and evaporated to dryness under reduced pressure at 35℃. The residue was redissolved in chloroform and subjected to GC-MS analysis. The mass spectrum (m/z: 404, 405, 406; 373, 374, 375; 345, 346, 347; 330, 331, 332; etc)indicates that the molecular ionic and fragment peaks of the metabolite all have 14 amu less than those of BDD. This means that the metabolite isolated is mono-O-demethylated BDD. The result confirmed our findings reported previously.     

应用HPLC同时测定大鼠尿中N,N-二(正丁基)阿霉素-14-戊酸酯及其8种代谢产物(英文)

目的,同时测定大鼠尿中N,N-二(正丁基)阿霉素-14-戊酸酯及其8种代谢产物 方法:建立了一种反相高压液相色谱法,大鼠iv 20mg·kg~(-1)原药后,其尿直接进样.梯度洗脱,荧光检测.结果:原药最低检出量2 ng,代谢物1—3 ng.被检物不受尿成分干扰.72 h尿中总葸环荧光信号仅为剂量的4.9％,其中主要为脱酰基以及N-脱丁基代谢物.6种次要代谢物包括苷元以及13—酮基还原性代谢物等,但未检出葡萄糖醛酸结合物.结论:本法简便易行,灵敏度高,特异性强。     

大戟根化学成分的研究

从中药大戟(Euphorbia pekinensis)根中分得9个化合物,经理化常数和波谱数据分析,分别鉴定为羊毛甾醇(I),3-甲氧基-4-羟基反式苯丙烯酸正十八醇酯(II),β-谷甾醇(III),伞形花内酯(IV),2,2′-二甲氧基-3,3′二羟基-5,5′-氧-6,6′-联苯二甲酸酐(V),d-松脂素(VI),槲皮素(VII),3,4-二甲氧基苯甲酸(VII)和3,4-二羟基苯甲酸(IX)。其中II和V为两个未见文献报道的新化合物,其余化合物均为首次从该植物中分离得到,VI为首次从该属植物中分得的木脂素类化合物。     

高效液相色谱-电喷雾串联四极杆质谱法研究大鼠尿内毛果芸香碱代谢产物

首次应用高效液相色谱-电喷雾串联四极杆质谱法鉴定了大鼠灌胃给予毛果芸香碱0.2mg后0-8小时内尿中的代谢物。4只大鼠给药毛果芸香碱盐酸盐,收集给药后尿液,固相萃取柱富集、然后应用高效液相色谱-电喷雾串联四极杆质谱法在线进行多反应监测,进而对尿中微量的代谢物进行了质谱解析。分别定性为毛果芸香碱的葡萄糖醛酸结合物、毛果芸香酸和毛果芸香酸的葡萄糖醛酸结合物。而且发现了各种代谢产物及原形药物在大鼠体内均有构型变化。     

LC/MSn鉴定咖啡酸在大鼠体内的代谢产物

目的 研究咖啡酸（CA）在大鼠体内的代谢产物。方法 大鼠灌胃（50 mg·kg-1）给予CA后采集0 ~ 4 h尿样,用电喷雾离子阱多级质谱法对CA在大鼠体内的代谢产物进行分析。结果 大鼠灌胃给予CA后,在体内可测到2个原形药的甲基化代谢物、2个原形药的单葡萄糖醛酸结合物、1个原形药的双葡萄糖醛酸结合物、2个原形药的单硫酸结合物、2个甲基化物的葡萄糖醛酸结合物和2个甲基化物的硫酸结合物。结论 CA在大鼠体内广泛代谢,其代谢物的结构有待于进一步分析后确证。     

隐丹参酮的吸收、分布、排泄和代谢

本文应用薄层层离法及双波长薄层色谱扫描仪分离及测定了生物样品中隐丹参酮的含量,并用此法研究了隐丹参酮在动物体内的吸收、分布和排泄过程。药物自胃肠道吸收后,大部分在体内转化。大鼠口服隐丹参酮后,胆汁中代谢产物随给药时间的延长逐渐增多。共得7个代谢产物。有隐丹参酮,丹参酮Ⅱ-A,丹参酮Ⅱ-A的羟基化产物及丹参酮Ⅱ-A与谷氨酸的缩合物等。有4个代谢产物有抑菌活性,但以原形药作用最强,后者可能是在动物体内发挥抗菌作用的主要形式。     

The metabolic fate of the dopamine agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin in rats after intravenous and oral administration. I. Disposition and metabolic profiling

1. The disposition and metabolic profiling of 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin(I), a dopamine agonist, were studied in anaesthetized rats after i.v. administration and in non-anaesthetized rats after i.v. and oral dosing. No major differences due to narcosis were observed. 2. Independent of dosing route or anaesthetic, clearance of I was rapid. Bile was the main route of excretion, accounting for 88% dose, compared with 9% in urine. 3. Drug metabolic profiling revealed that I is almost completely metabolized before elimination; less than 0.5% total radioactivity in bile and urine was due to parent compound. 4. The biliary metabolic profiles after i.v. and oral administration were similar. One major metabolite was detected, accounting for 50% (i.v.) or 65% (oral) dose. The major biliary metabolite was identified as the glucuronide of I. 5. Urinary metabolic profiles were quantitatively different from those of bile. After i.v. administration one major metabolite was detected in urine, but this was not the major biliary metabolite. After oral administration, the major urine metabolite was the same as the major biliary metabolite. These differences can be explained by first-pass gastro-intestinal metabolism.     

乙氧苯柳胺在家兔体内的主要代谢产物

采用高效液相色谱法对家兔口服乙氧苯柳胺（Ｎ－（４－乙氧苯基）－２－羟基苯甲酰胺）后在尿中的代谢物进行了分离与检测．用β－Ｄ－葡糖苷酸酶和该酶加专属性抑制剂葡糖二酸－１，４－内酯分别对尿样进行水解处理，发现该药的主要代谢物为β－Ｄ－葡糖醛酸结合物，其含量超过尿中代谢物总量的８０％．利用色谱保留值和紫外双波长吸收比对酶解后的主要生成物进行定性分析，证明该代谢物为乙氧苯柳胺葡糖醛酸结合物（Ｎ－（４－乙氧苯基）－苯甲酰胺－２－Ｏ－葡糖苷酸）．此外，在家兔给药后０～１２ｈ尿样中未检测出乙氧苯柳胺原形药物及其可能的代谢产物水杨酸．     

蒙古黄芪化学成分的分离鉴定

从蒙古黄芪(Astragalus membranaceus Bge.var.mongholicus(Bge.)Hsiao)乙醇提取物中分离得到10个单体,分别鉴定为棕榈酸(Ⅰ),羽扇醇(Ⅱ),β-谷留醇(Ⅲ),黄芪皂甙Ⅳ(astragaloside Ⅳ,Ⅳ),黄芪异黄烷甙(3S-(—)mucronulatol-7-D-glucopyranoside,Ⅴ),胡萝卜甙(Ⅳ),α-联苯双酯(dimethyl 4,4-dimethoxy-5,6,5′,6′-dimethylenedioxybiphenyl-2,2-dicarboxylate,(Ⅶ),天冬酰胺(Ⅷ),γ-氨基丁酸(Ⅸ),蔗糖(Ⅹ)。其中Ⅰ,Ⅱ和Ⅸ首次由蒙古黄芪巾分得,联苯双酯(Ⅶ)为已知合成物,但在天然药物黄芪中属首次分出,黄芪异黄烷甙(Ⅴ)未见报道。     

文冠果果壳中一个新生物碱

目的研究文冠果果壳的化学成分。方法通过硅胶柱色谱、制备型薄层色谱进行化合物的分离，利用多种波谱技术鉴定化合物结构。结果分离得到10个化合物，鉴定为：2-甲基-6-(2′，3′，4′-三羟基丁基)吡嗪(I)、cleomiscosin D(II)、柚皮素(III)、圣草素(IV)、山柰酚(V)、槲皮素(VI)、芦丁(VII)、5，7-二羟基色原酮(VIII)、酪醇(IX)、1-O-甲基-肌-肌醇(X)。结论化合物I为一新化合物；化合物II，IV，V和VII～X均为首次从该属植物中分离得到。     

DISPOSITION OF 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5 H )-FURANONE (MX) IN B6C3F1 MICE AND F344 RATS

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5 H )-furanone (MX) is a mutagenic by-product of chlorination of drinking water, particularly where the water contains humic matter. MX has been estimated to account for 50% of the mutagenic activity in some drinking water. A bioassay in rats demonstrated an increased tumor incidence, primarily in liver and thyroid glands. This study was designed to provide disposition/metabolism information in mice to evaluate the necessity of a National Toxicology Program chronic bioassay and to provide data for female rats. Radioactivity was rapidly absorbed and excreted near equally in urine (42-54%) and feces (40-51%) 72 h following oral administration of 14 C-labeled MX at single doses from 0.2 to 20 mg/kg to male and female mice and female rats. A larger percentage (71-73%) of MX-derived radioactivity was excreted in urine after an iv dose (0.2 mg/kg) in both female rats and male mice. Most MX-derived radioactivity was excreted within the first 24 h postdosing. MX was transformed to urinary and biliary metabolites. A major extremely polar urinary metabolite was tentatively identified as 1-hydroxy-1,2,2-ethanetricarboxylic acid. This metabolite is likely transformed from the MX degradation product 2-hydroxy-3-formyl-4-oxo-2-butenoic acid. Oral administration produced highest tissue/blood ratios in the following order: forestomach (>100), glandular stomach, intestine, and kidney. Intravenous administration resulted in high, prolonged levels of radioactivity in blood compared to oral dosing. Therefore, MX disposition appears to be dominated by its chemical reactivity with highest concentrations of radioactivity being found at the site of administration.     

The absorption, distribution, metabolism and excretion of rofecoxib, a potent and selective cyclooxygenase-2 inhibitor, in rats and dogs.

Absorption, distribution, metabolism, and excretion studies were conducted in rats and dogs with rofecoxib (VIOXX, MK-0966), a potent and highly selective inhibitor of cyclooxygenase-2 (COX-2). In rats, the nonexponential decay during the terminal phase (4- to 10-h time interval) of rofecoxib plasma concentration versus time curves after i.v. or oral administration of [(14)C]rofecoxib precluded accurate determinations of half-life, AUC(0-infinity) (area under the plasma concentration versus time curve extrapolated to infinity), and hence, bioavailability. After i.v. administration of [(14)C]rofecoxib to dogs, plasma clearance, volume of distribution at steady state, and elimination half-life values of rofecoxib were 3.6 ml/min/kg, 1.0 l/kg, and 2.6 h, respectively. Oral absorption (5 mg/kg) was rapid in both species with C(max) occurring by 0.5 h (rats) and 1.5 h (dogs). Bioavailability in dogs was 26%. Systemic exposure increased with increasing dosage in rats and dogs after i.v. (1, 2, and 4 mg/kg), or oral (2, 5, and 10 mg/kg) administration, except in rats where no additional increase was observed between the 5 and 10 mg/kg doses. Radioactivity distributed rapidly to tissues, with the highest concentrations of the i.v. dose observed in most tissues by 5 min and by 30 min in liver, skin, fat, prostate, and bladder. Excretion occurred primarily by the biliary route in rats and dogs, except after i.v. administration of [(14)C]rofecoxib to dogs, where excretion was divided between biliary and renal routes. Metabolism of rofecoxib was extensive. 5-Hydroxyrofecoxib-O-beta-D-glucuronide was the major metabolite excreted by rats in urine and bile. 5-Hydroxyrofecoxib, rofecoxib-3',4'-dihydrodiol, and 4'-hydroxyrofecoxib sulfate were less abundant, whereas cis- and trans-3,4-dihydro-rofecoxib were minor. Major metabolites in dog were 5-hydroxyrofecoxib-O-beta-D-glucuronide (urine), trans-3, 4-dihydro-rofecoxib (urine), and 5-hydroxyrofecoxib (bile).     

川芎哚大鼠体内代谢转化研究

目的　研究川芎有效成分川芎哚在大鼠体内的代谢转化。方法　分别ig川芎哚和［2-¹⁵N］川芎哚后,尿样经酶水解、碱化、有机溶剂提取。有机相(碱性和中性部分)经浓缩并硅烷化;水相经酸化、提取(提取物为酸性水溶部分)并硅烷化,用GC-MS测定。结果　在碱性和中性提取物中,检出原型川芎哚及其一种代谢物;在酸性水溶性提取物中,检出川芎哚的另两种代谢物。结论　川芎哚体内代谢途径可能是川芎哚羟基化和川芎哚羟甲基的氧化。