氨咖黄敏胶囊薄层色谱鉴别方法的改进

目的改进氨咖黄敏胶囊薄层色谱鉴别方法。方法采用TLC法对氨咖黄敏胶囊进行鉴别试验。结果TLC法同时检出了氨咖黄敏胶囊中对乙酰氨基酚、咖啡因、马来酸氯苯那敏3种成分。结论改进后的方法简便、灵敏、可行,分离效果好。     

薄层色谱法同时鉴别氨咖黄敏胶囊的三种成分

氨咖黄敏胶囊质量标准收载于《国家药品标准》。按鉴别（1）项下所述方法试验，鉴别样品中的对乙酰氨基酚与马来酸氯苯那敏，结果供试品与对照品的色谱相应位置上难以得到马来酸氯苯那敏的颜色斑点。该品种咖啡因的定性被列在鉴别（2）项，采用化学反应方法，操作繁琐，反应步骤多，耗时费力。为此本文通过试验，由硅胶GF254。板代替硅胶G板，并改进展开剂的组成，用薄层色谱法同时鉴别氨咖黄敏胶囊中对乙酰氨基酚、马来酸氯苯那敏、咖啡因，结果所得斑点均清晰明显，重复性好，稳定可靠。     

同时鉴定小儿氨咖黄敏颗粒中3种成分的薄层色谱法

目的建立同时鉴别小儿氨咖黄敏颗粒中3种成分的方法。方法采用薄层色谱法同时对小儿氨咖黄敏颗粒中的对乙酰氨基酚、马来酸氯苯那敏、咖啡因进行定性鉴别。结果与结论薄层色谱法准确、重现性好,可作为小儿氨咖黄敏颗粒的质量控制方法。     

氨咖黄敏胶囊鉴别方法的改进

氨咖黄敏胶囊(原名:速效伤风胶囊)是最常见的一种抗感冒药,每粒(片)含对乙酰氨基酚250mg,咖啡因15mg,马来酸氯苯那敏1mg,人工牛黄10mg.现收载于<国家药品标准>(化学药品地方标准上升国家标准第三册),对乙酰氨基酚和马来酸氯苯那敏已采用薄层色谱法鉴别,而对咖啡因的鉴别尚需提取、蒸干等,方法繁琐,费时.本文以薄层色谱法同时对对乙酰氨基酚、咖啡因、马来酸氯苯那敏3种成份进行鉴别;原标准中人工牛黄鉴别采用化学反应的方法,但专属性不强,颜色不明显,本实验也采用薄层色谱法,可鉴别人工牛黄中的胆酸、猪去氧胆酸两种成份,专属性强,斑点明显,操作简便快速,结果较为满意.     

氨咖黄敏胶囊中马来酸氯苯那敏的质量控制情况评价

目的建立氨咖黄敏胶囊胶囊中马来酸氯苯那敏的含量测定及含量均匀度检查方法,对9个厂家生产的氨咖黄敏胶囊中马来酸氯苯那敏的质量控制情况进行比较。方法高效液相色谱法,菲罗门Gemin-i C18(250mm×4.6mm,5μm),流动相:以磷酸盐缓冲液(磷酸二氢铵11.5g,加水溶解,加H3PO41mL,加水至1000mL)-乙腈(82∶18)为流动相,检测波长为262nm。结果马来酸氯苯那敏的线性范围为8.12～162.47mg·mL-1,r为0.9999。平均回收率为98.9%(RSD=0.8%)。结论经过质量比较说明,有必要对咖黄敏胶囊中马来酸氯苯那敏进行控制。     

HPLC法测定氨咖黄敏胶囊中对乙酰氨基酚、咖啡因的含量

氨咖黄敏胶囊是由对乙酰氨基酚、咖啡因、马来酸氯苯那敏、人工牛黄制成的复方制剂,收载于<国家药品标准>化学药品地方标准上升国家标准第三册[WS-10001-(HD-0276)-2002].标准[1]中对乙酰氨基酚、咖啡因均分别采用滴定法,提取操作麻烦、费时,且对乙酰氨基酚滴定终点判断易受主观影响,测量误差较大.本文采用HPLC法同时测定对乙酰氨基酚、咖啡因的含量.该方法简便、快速、准确,重现性好,使其含量测定结果准确可靠.     

HPLC法测定氨咖黄敏胶囊中马来酸氯苯那敏的含量

目的 建立测定氨咖黄敏胶囊中马来酸氯苯那敏含量的方法.方法 色谱柱为VP-ODS柱,流动相为甲醇-0.05 moL? L1磷酸二氢钾溶液(含三乙胺0.03％,用磷酸调pH至3.0)(43∶57),检测波长为215 nm,柱温为40℃,流速为1.0 mL?min-1.结果 马来酸氯苯那敏在20.24～48.57μg?mL-1浓度范围内线性关系良好,r=0.9998;平均回收率为99.78％,RSD=0.67％.结论 该方法专属性好,简捷、快速、准确,适用于氨咖黄敏胶囊中马来酸氯苯那敏含量的测定.     

HPLC法测定氨咖黄敏胶囊中对乙酰氨基酚、咖啡因、马来酸氯苯那敏的含量

目的:建立HPLC法测定氨咖黄敏胶囊中对乙酰氨基酚、咖啡因和马来酸氯苯那敏的含量;方法:色谱柱:Kromasil苯基柱(250 mm×4.6 mm,5μm);流动相:乙腈-水-三乙氨(20:79:1)(磷酸调pH至3.1),检测波长为260 nm;结果:线性范围:对乙酰氨基酚15.13～35.30μg,r=0.9999;咖啡因0.911～2.11μg,r=1.0000;马来酸氯苯那敏0.06～0.15μg,r= 0.9998;平均回收率:对乙酰氨基酚99.5%,RSD%=0.5%;咖啡因100.0%,RSD%=0.3%;马来酸氯苯那敏99.6%,RSD%=0.9%。结论:本方法简便、准确、灵敏度高、重现性好,可更好地控制本品质量。     

RP-HPLC测定氨咖黄敏胶囊中对乙酰氨基酚及咖啡因的含量

氨咖黄敏胶囊为解热镇痛药,常用于伤风感冒等诸多症状.处方中含对乙酰氨基酚、咖啡因、马来酸氯苯那敏、人工牛黄以及适量的辅料,成份较为复杂,已被国家药品标准收载.国家标准[1]中分别采用不同的方法测定对乙酰氨基酚和咖啡因的含量,操作繁琐,费时,误差来源多.本文采用HPLC法,对两种主要组分同时进行分离与检测,该法具有快捷,灵敏,分离度好等优点.     

氨咖黄敏片鉴别方法的改进及各主药含量的考察

氨咖黄敏片（速效伤风片）目前为临床比较流行的甲类OTC类抗感冒类药,其主药成分为对乙酰氨基酚、咖啡因、马来酸氯苯那敏及人工牛黄。质量标准收载与《国家药品标准》第三册,鉴别（1）为对乙酰氨基酚、马来酸氯苯那敏的薄层色谱鉴别,熏以碘蒸气显色,但斑点大小不好控制;     

Synthesis,characterization, and solvolysis of mono- and bis-S-(glutathionyl) adducts of methylene-bis-(phenylisocyanate) (MDI)

Bifunctional isocyanates are highly reactive compounds that undergo nucleophilic attack by a variety of functional groups available in the biological system. While the etiology of the respiratory disease caused by diisocyanates is not fully understood, a great deal of research has been performed to elucidate the chemical mechanisms involved in the direct and indirect effects of these compounds. Since adducts of isocyanates are found not only to proteins along the entire respiratory tree but also to proteins in the circulatory system, it is likely that a transport mechanism for the isocyanate from the respiratory to the circulatory system exists. The initial reaction of isocyanates with cellular thiols to form thiocarbamates, which are known to release the isocyanate under physiological conditions, is believed to provide a possible carrier mechanism for the isocyanate functional group. Previous work with aliphatic mono-isocyanates and the aromatic diisocyanate toluene diisocyanate has demonstrated the feasibility of this mechanism. Adding to this database, the products of the reaction of the highly water-insoluble, low vapor pressure, methylene-bis-(phenylisocyanate) (MDI) with glutathione were synthesized, and their chemical stability under various pH and buffer conditions was tested. Novel synthetic routes were developed for both the mono- and bis-S-(glutathionyl) adducts with MDI that yielded each compound in analytically pure form. Both compounds were found to be unstable under mild basic conditions (phosphate-buffered saline, pH 7.4, and NaHCO(3), pH 8.2), however to a different degree. Furthermore, a significant influence of the pH value (the rate of degradation increases with pH) and the concentration of free glutathione (increasing thiol stabilizes the adduct) on the stability was observed, indicating a base-catalyzed mechanism of the degradation/formation of the thiocarbamate bond. Unlike the monoadduct, which forms almost exclusively the polyurea upon degradation, a variety of products were formed upon degradation of the bis adduct. Though the disappearance of the bis adduct was complete as measured by HPLC, (1)H NMR spectra showed the existence of residual thiocarbamate bonds in the final mixture. In both cases, no evidence of the free methylene-bis-phenylamine (MDA) could be detected under the applicable conditions.     

In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites

Methadone and L-alpha-acetylmethadol (LAAM) are used as treatment for opiate addiction. Using a cellular model, we aimed to determine if methadone, LAAM and their main metabolites are substrates of the human P-glycoprotein transporter (P-gp), which is encoded by the ABCB1 gene, and whether methadone transport exhibits stereoselectivity. Pig kidney epithelial cells (control) and human ABCB1-transfected cells were incubated with methadone, LAAM and their metabolites, and their intra- and extracellular concentrations were measured. The intra- to extracellular ratios of methadone, LAAM and their metabolites were all decreased in ABCB1-transfected cells compared to controls (p < 0.05), thus indicating that they are substrates of P-gp. A weak stereoselectivity in methadone transport was observed towards the (S)-enantiomer. P-gp may therefore affect the pharmacokinetics and pharmacodynamics of methadone and LAAM.     

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in the Grenlandfjords (Norway)--disposition, levels, and effects

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are regarded as highly toxic. Their lipophilicity and persistence also render them subject to bioaccumulation. The Grenlandfjords (southern Norway) have long been polluted by PCDD/Fs through the magnesium production at Her?ya (1951-2002). Therefore, extensive environmental monitoring was performed in the area, and the project "Dioxins in the Grenlandfjords--DIG" was launched to study abiotic mass balances, biotic processes and ecological risk. This article describes some results from DIG on the dispositions of PCDD/Fs in the food web and biological effects. Furthermore, data from the Norwegian monitoring of the Grenlandfjords are described. Differences in cod liver PCDD/F levels were found between stations, with the highest concentrations in the inner fjord (the Frierfjord), closest to the pollution source. Furthermore, considerable decreases in the concentrations followed the large discharge reductions (1975 and 1990). Contrary to earlier food web studies on other organochlorines, it was found that the concentrations of PCDD/Fs decline with higher trophic level. Higher chlorinated congeners also constituted a lower percentage of sigmaPCDD/Fs higher in the food chain. The results indicated a limited bioaccumulation of PCDD/Fs, especially of higher chlorinated congeners, likely due to reduced membrane permeability (high molecular size), and possibly slow transport through intestinal aqueous phases. Hepatic cod 7-ethoxyresorufin O-deethylase (EROD) activities differed between the Frierfjord and the Eidangerfjord, showing the different PCDD/F exposure in the two fjords. Furthermore, seasonal variations in cytochrome P-450 (CYP) 1A activity were shown, with different responses between genders. The differences were likely linked to the reproductive cycle of the fish.     

Synthesis and anticholinesterase activity of (-)-N1-norphysostigmine, (-)-eseramine, and other N(1)-substituted analogues of (-)-physostigmine

(-)-N1-Benzylnorphysostigmine (4), prepared from synthetic (-)-O-methyl-N1-noreseroline (1) by N-benzylation, ether cleavage, and reaction of (-)-N1-benzylnoreseroline (3) with methyl isocyanate, was the intermediate used to prepare the title compounds. Catalytic debenzylation of 4 afforded (-)-N1-norphysostigmine (5), and (-)-eseramine (6) was obtained by reaction of 5 with methyl isocyanate. Reductive N-methylation of 5 gave (-)-physostigmine (9) while reaction of 5 with allyl bromide and phenethyl bromide afforded carbamates 7 and 8, respectively. Data on the in vitro potencies (IC50) and activities of certain of these compounds (4-8) as inhibitors of electric eel acetyl cholinesterase are reported. (-)-N1-Norphysostigmine (5) was found to be similarly potent against AChE as (-)-physostigmine (9).     

Terpenoid biotransformation in mammals IV Biotransformation of (+)-longifolene, (-)-caryophyllene, (-)-caryophyllene oxide, (-)-cyclocolorenone, (+)-nootkatone, (-)-elemol, (-)-abietic acid and (+)-dehydroabietic acid in rabbits

1. The metabolism of (+)-longifolene, (-)-caryophyllene, (-)-caryophyllene oxide, (-)-cyclocolorenone, (+)-nootkatone, (-)-elemol, (-)-abietic acid and (+)-dehydro-abietic acid was studied in rabbits.

2. Each of these sesquiterpenoids was converted to primary, secondary or tertiary alcohols, among which the primary alcohol was predominant.

3. A vinylic methyl group and an exomethylene group were easily hydroxylated and converted to a glycol via an epoxide in many cases.

4. Eight new metabolites were determined by chemical and spectroscopic methods.     

Analgesic and anti-inflammatory activities evaluation of (-)-O-acetyl, (-)-O-methyl, (-)-O-dimethylethylamine cubebin and their preparation from (-)-cubebin

The anti-inflammatory and antinociceptive effects of the acetylated (2), methylated (3) and aminated (4) derivatives of cubebin (1), obtained by its reaction with acetic anhydride, methyl iodide and dimethylethylamine chloride, respectively, were investigated, using different animal models. The compound (2) was the most effective anti-inflammatory one in the carrageenin-induced paw edema in rats and was the only one which showed dose-response correlation for this assay with r = 0.993 and Y = 64.58x + 0.22. Besides, compounds (2) and (4) were more effective than cubebin in inhibiting acetic acid-induced writhing in mice, producing dose-response correlation with doses of 10, 20 and 30 mg/kg, respectively. Regarding the hot plate and the cell migration tests in rats, none of the four tested compounds showed activity. Overall, the results showed that the acetylation and amination of cubebin were efficient in enhancing its analgesic activity, as well as its anti-inflammatory activity.     

Syntheses and cellular investigations of 17(3)-, 15(2)-, and 13(1)-amino acid derivatives of chlorin e(6)

A series of amino acid conjugates of chlorin e(6), containing lysine or aspartic acid residues in positions 17(3), 15(2), or 13(1) of the macrocycle were synthesized and investigated as photosensitizers for photodynamic therapy of tumors. All three regioisomers were synthesized in good yields and in five steps or less from pheophytin a (1). In vitro investigations using human carcinoma HEp2 cells show that the 15(2)-lysyl regioisomers accumulate the most within cells, and the most phototoxic are the 13(1) regioisomers. The main determinant of biological efficacy appears to be the conjugation site, probably because of molecular conformation. Molecular modeling investigations reveal that the 17(3)-substituted chlorin e(6) conjugates are L-shaped, the 15(2) and 13(1) regioisomers assume extended conformations, and the 13(1) derivatives are nearly linear. It is hypothesized that the 13(1)-aspartylchlorin e(6) conjugate may be a more efficient photosensitizer for PDT than the commercial currently used 15(2) derivative.