电喷雾离子阱质谱法直接测定几种药物的葡萄糖苷酸型代谢物

为研究药物代谢产物的质谱规律，用电喷雾离子阱质谱法对溶液中乙氧苯柳胺、ＳＦＺ４７羧基衍生物、５羟基普罗帕酮及普罗帕酮的βＤ葡萄糖苷酸型代谢物的结构进行了测定。结果表明，它们的（－）ＥＳＩＭＳ均生成［Ｍ－Ｈ］－准分子离子，（－）ＥＳＩＭＳ２和（－）ＥＳＩＭＳ３则分别生成ｍ／ｚ１７５和ｍ／ｚ１１３碎片离子。提示这些共同特征可用于ＬＣ／ＭＳ法直接分析药物的葡萄糖苷酸型代谢物     

微生物来源的胆固醇生物合成酶抑制研究：Ⅲ.抗生素SIPI—891…

ＳＩＰＩ－８９１５经ＳＩＰＩ－１８６菌生物转化得１种转化产物，其结构经紫外，质谱（ＥＩ，ＨＲＭＳ），＾１Ｈ－ＮＭＲ，＾１Ｈ－＾１Ｈ ＣＯＳＹ，＾１３Ｃ－ＮＭＲ（ＤＥＰＴ），＾１３Ｃ－＾１Ｈ ＣＯＳＹ等光谱分析，证实该转化产物的结构与ｐｒａｖａｓｔａｔｉｎ相同。     

家兔尿中SFZ-47及其两种主要代谢产物的HPLC定量方法

家兔尿中ＳＦＺ┐４７及其两种主要代谢产物的ＨＰＬＣ定量方法顾景凯钟大放翟志慧建立了家兔尿中ＳＦＺ－４７及其两种主要代谢产物ＳＦＺ－４７羧基衍生物（Ｍ１）及该衍生物的酯型β－Ｄ－葡糖苷酸（Ｍ２）的ＨＰＬＣ测定方法，并用该法对单剂量口服２３０ｍｇＳＦＺ－...     

微生来源的胆固醇生物合成酶抑制剂：Ⅷ.抗生素SIPI—891 …

真菌ＳＩＰＩ－８９１７蓖株的代谢产物具有抑制胆固醇生物合成酶活性，对其代谢产物进一步研究，应用丙酮浸泡，溶媒萃取，硅胶柱分离和ＬＨ２０凝胶层析等方法，从其菌丝体中分离出另一种化合物，命名为ＳＩＰＩ－８９１７－Ⅴ。根据质谱（ＥＩ－ＭＳ、ＦＡＢ和ＨＲＭＳ）数据，确定其分子式为：Ｃ２８Ｈ４４Ｏ１（分子量：３９６．３３７０），综合紫外光谱、红外光谱、＾１Ｈ－ＮＭＲ、＾１３Ｃ－ＮＭＲ及ＨＭＢＣ和ＨＭＱＣ等图     

银杏叶及其制剂中萜内酯含量测定方法研究进展

综述了国内外银杏叶及其制剂中萜内酯含量测定方法研究概况。主要采用ＲＰ－ＨＰＬＣ－ＵＶ,ＲＰ－ＨＰＬＣ－ＲＩ,ＲＰ－ＨＰＬＣ－ＥＬＳＤ,ＳＦＣ－ＥＬＳＤ和ＧＣ－ＦＩＤ,以及与ＭＳ联机的ＲＰ－ＨＰＬＣ－ＴＳＰ－Ｍ,ＧＣ－ＥＩ－ＭＳ色谱分析法,此外尚有ＮＭＲ,ＣＥ,ＴＬＣＳ及生物测定法。这些研究大都是在９０年代进行的,其中ＧＣ－ＦＩＤ与ＲＰ－ＨＰＬＣ－ＥＬＳＤ法较为成熟,可行,前者作为生物样品测定具有够     

微生物来源的胆固醇生物合成酶抑制剂研究Ⅲ．抗生素SIPI─8915转化产物的研究

ＳＩＰＩ－８９１５（ｃｏｍｐａｃｔｉｎ）经ＳＩＰＩ－１８６菌株生物转化得１种转化产物，其结构经紫外、质谱（ＥＩ，ＨＲＭＳ）、１Ｈ－ＮＭＲ、１Ｈ－１ＨＣＯＳＹ、１３Ｃ－ＮＭＲ（ＤＥＰＴ）、１３Ｃ－１ＨＣＯＳＹ等光谱分析，证实该转化产物的结构与ｐｒａｖａｓｔａｔｉｎ相同     

微生物来源的胆固醇生物合成酶抑制剂 Ⅷ.抗生素SIPI-8917-Ⅴ的研究

真菌ＳＩＰＩ－８９１７菌株的代谢产物具有抑制胆固醇生物合成酶活性，对其代谢产物进一步研究，应用丙酮浸泡、溶媒萃取、硅胶柱分离和ＬＨ２０凝胶层析等方法，从其菌丝体中分离出另一种化合物，命名为ＳＩＰＩ－８９１７－Ⅴ。根据质谱（ＥＩ－ＭＳ、ＦＡＢ和ＨＲＭＳ）数据，确定其分子式为：Ｃ２８Ｈ４４Ｏ１（分子量：３９６．３３７０），综合紫外光谱、红外光谱、１Ｈ－ＮＭＲ、１３Ｃ－ＮＭＲ及ＨＭＢＣ和ＨＭＱＣ等图谱数据的解析，确定其结构为甾醇类化合物，旋光活性研究表明：与文献报道的麦角甾醇（ｅｒｇｏｓｔｅｒｏｌ）结构一致，化学命名为：麦角－５，７，２２Ｅ－三烯－３β－醇（ｅｒｇｏｓｔａ－５，７，２２Ｅ－ｔｒｉｅｎ－３β－ｏｌ）。     

右旋黄皮酰胺在大鼠肝微粒体中的代谢转化

目的：研究黄皮酰胺的主要代谢途径,为进一步研究黄皮酰胺代谢的立体选择性打下基础。方法：用大鼠肝微粒体体外温孵法对右旋黄皮酰胺((+)-clausenamide)进行温孵,用硅胶柱色谱、制备TLC分离纯化代谢产物并通过光谱分析鉴定其结构。结果：分离得到5个代谢产物CM1,CM3,CM4,CM5及CM6,其结构分别鉴定为6-羟基,4-羟基,4,6-二羟基,4-苯环邻位羟基,4,7-苯环间位-二羟基黄皮酰胺。结论：黄皮酰胺的代谢主要发生羟化或双羟化,CM3是其主要代谢产物,量较少的CM4,CM6为其进一步代谢产生的双羟基代谢产物;另2个代谢产物CM1,CM5产生的量也较少;CM2未分离得到,但通过HPLC分析知其为右旋黄皮酰胺的微量代谢产物。     

2－甲基－4（5）－硝基咪唑合成的改进

２－甲基－４（５）－硝基咪唑合成的改进蔡汉民，刘传生，蔡蔚（石家庄市新华制药厂，河北０５００９１）ＩＭＰＲＯＶＥＤＳＹＮＴＨＥＳＩＳＯＦ２－ＭＥＴＨＹＬ－（５）－ＮＩＴＲＯＩＭＩＤＡＺＯＬＥ￥ＣＡＩＨａｎ－Ｍｉｎ；ＬＩＵＣｈｕａｎ－Ｓｈｅｎｇ；ＣＡＩ...     

微生物来源的胆固醇酰基转移酶抑制剂研究：Ⅱ.NA—A,B的 …

从曲霉Ｈ７１７的发酵产物中分离得到两个脂酰辅酶胆固醇酰基转移酶（ＡＣＡＴ）的抑制剂,根据ＥＩ－ＭＳ、ＦＡＢ－ＭＳ和ＨＲＥＩ－ＭＳ数据,确定其分子式分别为Ｃ２７Ｈ３３Ｎ３Ｏ７（分子量：５１１．２）和Ｃ２７Ｈ３３Ｎ３Ｏ５（分子量：４７９．２）。综合紫外光谱、质谱、核磁共振光谱和Ｘ－结晶衍射等数据解析,确定其结构为含有吲哚环的二酮哌嗪类化合物。与文献对照,其中ＮＡ－２０９Ａ为ｖｅｒｒｕｃｕｌｏｇｅｎ的立     

左旋黄皮酰胺在大鼠肝微粒体中的代谢转化研究

用大鼠肝微粒体体外温孵法进行了左旋黄皮酰胺[(-)-clausenamide]代谢转化研究,优化了温孵体系,建立了反相HPLC-DAD同时分离检测左旋黄皮酰胺及其体外代谢产物的分析方法。用硅胶低压柱色谱、制备TLC及制备HPLC分离纯化了两个代谢产物并进行了光谱鉴定。结果表明,两个代谢物分别确定为6-和5-位羟基取代的黄皮酰胺。     

左旋黄皮酰胺在大鼠体内的排泄

左旋黄皮酰胺[（-）-clausenamide]是从芸香科黄皮属植物黄皮[Clausena lansium（lour） sheels]叶的水浸膏中分离得到的有效成分，经不对称合成和拆分制备而得。药效学研究表明，左旋黄皮酰胺促进突触体谷氨酸释放，增加大鼠脑皮层厚度和海马CAL区突触数及NMDA受体密度，提高小鼠脑皮层和海马的胆碱乙酰转移酶活性，对抗樟柳碱引起的乙酰胆碱含量降低。这些结果表明左旋黄皮酰胺具有较好的促智和神经保护作用以及潜在的抗老年痴呆作用；右旋体作用不明显，且有较强的毒性。     

左旋一叶碱的代谢转化

目的研究一叶碱［securinine,(-)SE］在大鼠体内外的代谢转化。方法采用大鼠肝微粒体体外温孵法对(-)SE的代谢转化进行了研究,优化了代谢体系,建立了反相HPLC法同时分离检测(-)SE及其体外代谢产物的分析方法。用液液萃取,制备TLC及半制备HPLC分离纯化了4个代谢产物并进行了光谱鉴定。在此基础上,建立了生物体液中(-)SE及其代谢物的反相HPLC分析方法,并用该法检测了ip给药后大鼠的胆汁、尿样及其经β-葡糖醛酸苷酶水解后的样品。结果代谢物分别鉴定为6-位羟基,6-位羰基及5-位α及β羟基取代的(-)SE,还证实了体内6-位羟基代谢物进一步形成了二相结合型产物。结论基本阐明(-)SE在大鼠体内外代谢转化的途径。     

LC-MS/MS法研究1-[1-(6-甲氧基-2-萘基)乙基]-2-(4-硝基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐在大鼠体内的代谢产物

采用液相色谱-串联质谱法对大鼠灌胃1-［1-(6-甲氧基-2-萘基)乙基］-2-(4-硝基苄基)-6,7-二甲氧基-1,2,3,4-四氢异喹啉氢溴酸盐(编号P91024)后粪便、尿液、胆汁和血浆中的主要代谢产物进行研究。通过比较给药样品和空白样品的全扫描总离子流色谱和选择离子扫描色谱图差别寻找I相代谢产物；根据其一级和二级质谱图，确定I相代谢产物的分子结构。完全提取I相代谢产物后的样品溶液，再用葡糖醛酸酶酶解，得II相结合物的苷元部分，采用与I相代谢产物鉴定同样方法寻找和鉴定II相代谢产物苷元的结构，进而确证II相代谢产物的分子结构。从大鼠粪便中鉴定出P91024的2个I相代谢物，从胆汁中鉴定出1个I相和5个II相代谢产物，从尿液中鉴定出1个I相和3个II相代谢产物，从血浆中鉴定出4个I相和1个II相代谢产物；并分别分析推测出它们的结构。P91024在大鼠体内被代谢转化为多种产物，利用LC-MS/MS可以快速寻找和鉴定。     

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。     

Determination of urinary 2-mercaptobenzothiazole (2-MBT), the main metabolite of 2-(thiocyanomethylthio)benzothiazole (TCMTB) in humans and rats

 A method for biological monitoring of urinary 2-(thiocyanomethylthio)benzothiazole (TCMTB), a wood preservative and an industrial chemical, was developed. Three different doses of TCMTB in olive oil were given to male rats by gavage for 3 weeks. Urine was collected daily and the metabolites were analysed as thioethers by derivatization with pentafluorobenzylbromide by gas chromatography-mass spectrometry. The parent chemical was not detected in urine samples, but two metabolites of TCMTB were identified. 2-Mercaptobenzothiazole (2-MBT) was the main metabolite, and its excretion varied according to the dose. The second metabolite was 2-(mercaptomethylthio)benzothiazole. The amount of 2-MBT excreted in rat urine was 66±12% (SD), 51±20% and 44±9% for TCMTB doses of 15, 75 and 150 mg/kg, respectively. Two doses, 75 and 150 mg/kg, caused diuresis in rats during the 1 week of dosing. During the 3-week TCMTB treatment, rat liver microsomal CYP enzyme profile was not significantly changed. Urine samples of sawmill workers exposed to TCMTB were collected after their work shifts for exposure assessment. TCM-TB could not be detected in the urine samples of exposed workers. Most concentrations of 2-MBT were below the limit of the detection, 0.12 μmol/l, the concentrations were 0.12–0.15 μmol/l only in few cases. The determination of 2-MBT in urine, when a sample is taken immediately after a work shift, is a suitable indicator of workers’ exposure to TCMTB. Received: 15 September 1995/Accepted: 30 January 1996     

Comparison of benzo(a)pyrene metabolism by testicular homogenate and the isolated perfused testis of rat following 2,3,7,8-tetrachlorodibenzo-P-dioxin treatment

Benzo(a)pyrene (BP) metabolism was studied in the cell free testicular homogenate and in the isolated perfused rat testis 72 h following tetrachlorodibenzo-P-dioxin (TCDD). The BP concentration for both metabolic systems was 2 × 10^–7 M. BP metabolites were extracted from testicular homogenate, perfusate and testicular tissue and subjected to high-pressure liquid Chromatographic analysis. The ratio of various BP metabolites in the cell free homogenates ranged from 3.5 to 164 times those of the isolated perfused testis, and the total BP metabolites in the cell free system of either control or TCDD-induced testis were 16 times that of the intact isolated perfused testis. The major BP metabolites in the organic extractable phase from the isolated perfused testis and the testicular homogenate were BP dihydrodiols and BP phenols, respectively.The ratio of water soluble metabolites to organic soluble metabolites in the homogenate and the isolated perfused testis is 1.1 and 3.0 respectively. Therefore, in the intact isolated testis, water soluble BP metabolites are formed three times greater than those of the organic soluble BP metabolites, and thus suggests that specific conjugating enzyme activities in the intact testis are greater than those of the homogenates. The magnitude of various BP metabolites in either the homogenates or the isolated perfused testis of TCDD treated rats ranged from 1.4 to 2.2 times their respective controls, except 4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene in the isolated perfused testis was not altered by TCDD treatment. In conclusion, the isolated perfused rat testis is metabolically active and capable of biotransforming PAH. This system better reflects metabolic capability of the intact organ in the rats than do cell free homogenate system. The isolated perfused testis system retains the integrity of the complex biological organization of tissues, cell types, and enzymes in testicular metabolism and may provide data that may aid in the prediction of germ cell mutation as well as toxicity.The Abbreviations Used are PAH polycyclic aromatic hydrocarbons - BP benzo(a)pyrene - 9,10-diol 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene - 7,8-diol 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene - 4,5-diol 4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene - 3-OH 3-hydroxybenzo(a)pyrene - 9-OH 9-hy-droxybenzo(a)pyrene - 7-OH 7-hydroxybenzo(a)pyrene - 12-OH 12-hydroxybenzo(a)pyrene - 1,6-quinone benzo(a)pyrene-1,6-dione - 3,6-quinone benzo(a)pyrene 3,6-dione - 6,12-quinone benzo(a)pyrene 6,12-dione - DMBA 7,12-dimethylbenzanthracene - DMN dimethylnitrosamine - 7,8-diol 9,10-epoxide 5,7-t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene - HPLC high pressure liquid chromatography - TCDD 2,3,7,8-tetrachlorodibenzo-P-dioxin - HEPES N-2-hydroxyethylpiperazine-N-2-ethane sulfonic acid - NADP⁺ nicotinamide adenine dinucleotide - AHH aryl hydrocarbon hydroxylase - EH epoxide hydrolase - GSH-T glutathione transferase - HPRT hypoxanthine phosphoribosyltransferase     

New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP

The metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans was studied after three doses of 0.35 mg (4.7 g/kg), 2.15 mg (28.7 g/kg) and 48.5 mg (650 g/kg) of D4-ring-labelled DEHP were administered orally to a male volunteer. Two new metabolites, mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) and mono[2-(carboxymethyl)hexyl]phthalate (2cx-MMHP) were monitored for 44 h in urine and for 8 h in serum for the high-dose case, in addition to the three metabolites previously analysed: mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP). For the medium- and low-dose cases, 24 h urine samples were analysed. Up to 12 h after the dose, 5OH-MEHP was the major urinary metabolite, after 12 h it was 5cx-MEPP, and after 24 h it was 2cx-MMHP. The elimination half-lives of 5cx-MEHP and 2cx-MMHP were between 15 and 24 h. After 24 h 67.0% (range: 65.8–70.5%) of the DEHP dose was excreted in urine, comprising 5OH-MEHP (23.3%), 5cx-MEPP (18.5%), 5oxo-MEHP (15.0%), MEHP (5.9%) and 2cx-MMHP (4.2%). An additional 3.8% of the DEHP dose was excreted on the second day, comprising 2cx-MMHP (1.6%), 5cx-MEPP (1.2%), 5OH-MEHP (0.6%) and 5oxo-MEHP (0.4%). In total about 75% of the administered DEHP dose was excreted in urine after two days. Therefore, in contrast to previous studies, most of the orally administered DEHP is systemically absorbed and excreted in urine. No dose dependency in metabolism and excretion was observed. The secondary metabolites of DEHP are superior biomonitoring markers compared to any other parameters, such as MEHP in urine or blood. 5OH-MEHP and 5oxo-MEHP in urine reflect short-term and 5cx-MEHP and 2cx-MMHP long-term exposure. All secondary metabolites are unsusceptible to contamination. Furthermore, there are strong hints that the secondary oxidised DEHP metabolites—not DEHP or MEHP—are the ultimate developmental toxicants.     

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。     

Identification of etazene (etodesnitazene) metabolites in human urine by LC-HRMS

Etazene (or etodesnitazene) is a novel and highly active synthetic opioid belonging to the rapidly evolving and emerging group of “nitazenes.” Etazene metabolites were identified through analysis of a human urine sample. The sample was obtained from a 25-year-old man who attempted suicide by taking a new psychoactive substances (NPS) cocktail purchased online and was analyzed by ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Etazene metabolites were predicted with BioTransformer 3.0, and the exact masses were added to the inclusion list. Eight possible metabolites were identified in the urine sample. N- and O-deethylation were identified as the predominant metabolism routes, resulting in M1 (O-deethylated etazene; most abundant metabolite based on the peak area), M2 (N-deethylated etazene), and M3 (N,O-dideethylated etazene) metabolites. Less abundant hydroxylated products of these deethylated metabolites and etazene were also found. Additionally, in the analysis without β-glucuronidase treatment, M1- and M3-glucuronide phase II metabolites were found. As N- and O-deethylated products seem to be the predominant urinary metabolites, the detection of these metabolites in urine can be useful to demonstrate etazene exposure.