主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA

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  • 2015 Volume 46 Issue 1
    Published: 10 January 2015
      

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  • SUN Huafu1,3, YANG Yanyin2*, YE Wenrun1
    2015, 46(1): 4-6.
    Abstract ( )   Knowledge map   Save
    Methylnaltrexone bromide was synthesized from naltrexone hydrochloride via condensation with ethylene glycol, etherification with t-butyldimethylchlorosilane and methylation with methyl iodide to give (R)-3-[(tbutyldimethylsilyl) oxy]-17-cyclopropylmethyl-4,5a-epoxy-14-hydroxy-6-(1,3-dioxolane-2-yl)-N- methylmorphinanium iodide, which was subjected to hydrolysis with hydrobromic acid, ion exchange with bromide anion exchange resin. The overall yield was about 53% and HPLC purity was more than 99%.
  • LI Haisu, ZOU Shenglan, DONG Liang, CHEN Guoliang*
    2015, 46(1): 10-12.
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    Imidafenacin was obtained from diphenylacetonitrile via substitution with 1,2-dibromoethane, condensation with 2-methylimidazole to give 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutyronitrile, which was subjected to salt formation with hydrochloric acid and hydrolysis with potassium hydroxide with the overall yield of 51.2% and the HPLC purity of 99.5%. The main impurity 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanoic acid was synthesized from imidafenacin via hydrolysis with potassium hydroxide with the HPLC purity of 98%.
  • YAO Lan, GE Han, SHEN Shunyi*
    2015, 46(1): 13-16.
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    Twelve new 3-O-decladinosyl-3-oxo-9-substituted azine clarithromycin derivatives were synthesized from clarithromycin. The antibacterial activities of the title compounds were tested in vitro and the results showed that these compounds exhibited good antibacterial activities against the tested gram-positive bacteria including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus albus, Diplococcus lanceolatus and Gamma streptococcus.
  • SONG Bo1, ZHANG Zhiwei2, LI Ridong1*, WANG Wenfeng1
    2015, 46(1): 17-19.
    Abstract ( )   Knowledge map   Save
    The degradation impurity of pramipexole, BI-IO460BS, was synthesized from pyroglutaminol by substitution with 4-toluene sulfonyl chloride, cyanation with potassium cyanide, N-alkylation with 1-iodine propane, methyl esterification, sulfuration with Lawesson's reagent, substitution with cyanamide and hydrolysis. The total yield was 5.9%. Its structure was confirmed by MS and 1H NMR.
  • CAI Shuangming, WU Yong, HUANG Zongqing, FENG Jun*
    2015, 46(1): 20-23.
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    One of the secondary metabolites of strain SIPI-2013406 was purified through anion exchange resin and reverse-phase C18 chromatographic column with purity over 98%. Its structure was elucidated as fumaryl-L-alanine by MS and NMR analysis. After the morphological and molecular characterization, the strain SIPI-2013406 was identified as Penicillium chrysogenum.
  • WU Jinxia1, WU Hongyue1, SHAN Biao2, ZHANG Heying3*
    2015, 46(1): 24-26.
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    Kunming mice were fed with high-level lipid feeds to establish the hyperlipidemic mouse models. The mice were treated with earthworm lyophilized powder at dosages of 0.4, 0.2 and 0.1 g/kg once a day, meanwhile they were fed with high-level lipid feeds for 10 weeks. The total RNA of liver were extracted, and the changes of liver hydroxymethylglutaryl CoA reductase (HMG-CoAR) gene expression were analyzed by RT-PCR. The results indicated that earthworm lyophilized powder down-regulated HMG-CoAR mRNA expression markedly, suggesting that the effect of earthworm lyophilized powder on reducing serum cholesterol in hyperlipidemic mice was probably involved in downregulating HMG-CoAR mRNA expression.
  • BAO Xiaoyue1, JIANG Shijun2, DAN Zhaoling2, XU Leilei2, CHEN Dawei1*
    2015, 46(1): 27-31.
    Abstract ( )   Knowledge map   Save
    The probucol solid self-microemulsion (1-SSME) with mean particle size of 27 nm was prepared by grinding method. The results of differential scanning calorimetry and X-ray diffraction analyses showed that the drug existed in an amorphous status in the 1-SSME. In 0.1 mol/L hydrochloric acid and pH 6.8 phosphate buffer, the dissolutions at 1 h of 1-SSME were 56% and 66%, respectively. Compared with the bulk drug, the cmax and AUC of 1-SSME in rats were significantly improved. The relative bioavailability of 1-SSME was 350%.
  • LI Muyong1, YANG Cheng2, PENG Qiang3*
    2015, 46(1): 32-34.
    Abstract ( )   Knowledge map   Save
    To improve the dissolution of piroxicam(1), the micronized 1 and the solid dispersion of 1 with Plasdone S630 as carrier were prepared. Then the tablets based on micronized drug or solid dispersion were prepared and their pharmacokinetics in Beagle dogs were evaluated with commercial 1 tablets as reference preparation. The results showed that micronization had little effect on the improvement of pharmacokinetic behavior of 1, while forming solid
    dispersion could significantly enhance its oral bioavailability. Compared with the reference tablets, the relative oral bioavailability of tablets based on micronized 1 was 103.6%, while the relative bioavailabilities of the tablets based on solid dispersion of 1-Plasdone S630 in the ratio of 1∶3 and 1∶5 were 128.9% and 138.9%, respectively.
  • TAN Yueyao, YAN Yongdong, LI Aizhen
    2015, 46(1): 35-39.
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    The formulation of capsule shell materials was optimized by orthogonal design with contents of ethanol and 1,2-propanediol and dissolution of cyclosporine A as indexes. The preparation was also optimized according to the results of stability test. The results showed that adding polyols to the capsule shell materials and preparing under relative humidity of 25% with slow drying speed within 40 h to control the rubber moisture of 8% could obtain the soft
    capsules with rather stable properties. Compared with the commercial cyclosporine A soft capsules, the migration amount of ethanol from the content of the prepared soft capsules was decreased while the dissolution behavior of cyclosporine A from the capsules was similar. The results of pharmacokinetics in Beagle dogs showed that these two preparations were bioequivalent.
  • LUO Lijuan1, HU Yanchun1*, SHU Gang1, LAN Lan2, JIANG Zhongrong2
    2015, 46(1): 40-43.
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    The enteric microcapsules loaded with five hydrated ferric citrate were prepared by emulsion solvent evaporation method with acrylic resin Ⅱ as coating material. The formulation was optimized by response surface methodology with encapsulation efficiency as the index. The optimal formulation was as follows: 0.26 g of five hydrated ferric citrate, 160 ml of liquid paraffin, 0.32 g of talcum powder and 0.68 g of Span-80. A flame atomic absorption spectrometry was established for the determination of iron in the microcapsules. The results showed that the optimal product was smooth and spherical with mean particle size of 240 μm. The drug loading and encapsulation efficiency were 21.5% and 94.1%. The dissolution within 120 min in hydrochloric acid (pH 1.0) of the product was less than 10% while in pH 6.8 phosphate buffer was about 80%.
  • ZHAO Xi1,2, KANG Hui1,2, YANG Hanyu1,2*, WANG Manman1,2, GAO Na1,2
    2015, 46(1): 44-47.
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    A LC-MS/MS method was established for the determination of atorvastatin (1) and its active metabolites, ortho-hydroxy-atorvastatin (2) and para-hydroxy-atorvastatin (3), in human and Beagle dog plasma after oral administration of atorvastatin calcium tablets. The pharmacokinetic parameters of 1, 2 and 3 were calculated and compared. The results indicated that the parent drug 1 was the main format circulated in human bodies, and the active metabolite 3 was not detected. While in Beagle dogs, the active metabolite 2 was the main format, with co-existence of parent drug 1 accounting for 30% as well as metabolite 3 accounting for 5%. The half life time of 1 in human bodies was about three times as long as that in Beagle dogs, while its clearance in human bodies was about 65% of that in Beagle dogs. In conclusion, there were significant pharmacokinetic differences of 1 between human and Beagle dogs. Both
    metabolism velocity and extent of parent drug in Beagle dogs were significantly higher than those in human bodies.
  • HUANG Ming, ZHANG Quanying*, WANG Meng
    2015, 46(1): 48-51.
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    An LC-MS/MS method was established for the determination of rebamipide in human plasma to evaluate the pharmacokinetics and bioequivalence of rebamipide dispersible tablets(test preparation) in healthy volunteers. A single oral dose of two rebamipide preparations[test tablets vs. commercial tablets(Mucosta®), reference preparation] was given to 22 healthy male volunteers according to a randomized crossover design. Drug plasma concentrations were
    determined by LC-MS/MS after deproteinized with acetonitrile. The pharmacokinetic parameters were calculated by DAS2.1.1 software. The main pharmacokinetic parameters of rebamipide in test and reference preparations were as follows: cmax(236.9±103.4) and (233.9±105.1)ng/ml, tmax(2.7±1.1) and (2.9±1.4)h, t1/2(2.0±0.8) and (2.3±1.5)h, AUC0→12 h(929.0±291.9) and (970.5±353.2)ng·h·ml-1, respectively. The relative bioavailability of test formulation was (102.6±29.8)%.
  • ZHANG Mengmeng, PAN Hongjuan*, CHEN Jia, LIU Xiaohui
    2015, 46(1): 55-58.
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    A derivative headspace capillary GC method using electron capture detector (ECD) was established for the determination of methyl, ethyl and isopropyl methanesulfonate (MMS, EMS and IMS) in dapoxetine hydrochloride. A PW-5 capillary column was used, with sodium iodide as the iodonation agent, nitrogen as the carrier gas, and ECD as the detector in temperature program mode. The calibration curves for MMS, EMS and IMS were linear in the ranges of 0.03 - 0.30, 0.05 - 0.50 and 0.05 - 0.50 μg/ml, respectively. Their average recoveries were 63.5%, 100.3% and 96.2%, with LLODs of 0.30, 0.50 and 0.50 ng/ml, respectively.
  • XU Mingming, ZHENG Luxia, SHAO Hong, CHEN Gang*
    2015, 46(1): 59-61.
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    A capillary zone electrophoresis method was established for the determination of acetates and phosphates in amino acid injection. An uncoated fused silica capillary column was used with pyridine-dicarboxylic acid (pH 5.6) as the electrophoresis buffer, at the separation voltage of 30 kV, the detection wavelength of 232 nm, and the pressure injection of 10 s (0.7 psi). The calibration curves of acetates and phosphates were linear in the ranges of 0.360 - 9.002 mmol/L and 0.073 - 1.815 mmol/L, respectively. Their average recoveries were 100.74% and 100.70%, with RSDs of 0.88% and 1.55%.
  • YANG Benxia1, ZHENG Zidong1, ZHAO Yongqiang2
    2015, 46(1): 62-64.
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    An HPLC method combined with a GC method was established for the determination of the related substances in chlorcyclizine hydrochloride. N-Methylpiperazine, a known related substance in chlorcyclizine hydrochloride, was determined by GC. A Rtx-1 capillary column was used with the application of temperature program and flame ionization detector. It was linear for N-methylpiperazine in the range of 10 - 100 μg/ml. The average recovery was 99.3%, with RSD of 1.3%. Its low limit of detection was 0.22 μg/ml. Other unknown related substances were determined by HPLC. A C18 column was used, with the mobile phase of acetonitrile∶0.01 mol/L potassium dihydrogen phosphate solution (containing 0.4% triethylamine, adjusted with phosphoric acid to pH 3.5) (35∶65) at the detection wavelength of 231 nm. Chlorcyclizine hydrochloride could be separated well with its degradation products.
  • ZHANG Xinxin, YANG Yang, LIU Jianli, WANG Yan, SUN Wenji*
    2015, 46(1): 65-67.
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    The fingerprint of steroid saponins from Di'aoxinxuekang capsules was established by HPLC-ELSD method. An Inersil ODS-3 column was used, with the mobile phase of acetonitrile∶0.1% formic acid by gradient elution, with the application of evaporative light scattering detector (ELSD). The common pattern fingerprint of steroid saponins was established after examining 11 batches of Di'aoxinxuekang capsules, and their similarities were 0.934 - 0.998. There
    were 8 common peaks, in which two of them were identified as protodioscin and dioscin using the reference compounds.
  • GU Xueqin1,2, FAN Guorong1, LU Feng1, QI Yunpeng1*
    2015, 46(1): 68-73.
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    Metabolomics is a branch of system biology developed in recent years. It aims to reveal the variation of endogenous metabolic profiles in biological samples, such as body fluids, cells, and tissues, when subjected to external stimuli. Gas chromatography-mass spectrometry (GC-MS) has high resolution and detection sensitivity, with a standard spectral library to facilitate identification of endogenous metabolites. Thus, GC-MS has been widely employed in metabolomics. This review introduces key technologies in GC-MS based metabolomics, including derivatization, identification of metabolites, and data analysis. Meanwhile, typical applications in GC-MS metabolomics describing metabolic profiles of low-molecular-weight metabolites, such as amino acids, fatty acids, organic acids, and sugars are described.
  • LI Shasha, SUN Pengchao, HUANG Weiwei, HAN Mengmeng, ZHAO Yongxing*
    2015, 46(1): 97-101.
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    Due to the complexity of ocular physiological structure and the existence of numerous barriers, many drugs have little effect on the eye diseases. To improve the therapy efficacy of ophthalmic drugs, colloidal systems (including nanosuspensions, liposomes, micro-/nano- emulsions, fat emulsions and nanoparticles), in situ gel and solid preparation for ophthalmic delivery are adopted to prolong drug corneal retention and reduce the systemic absorption.
    This paper reviews the recent advances of above drug delivery systems, but also points out some obstacles.
  • HAN Shilei1, ZHAO Shiming2*, LUO Zhenfu2
    2015, 46(1): 102-106.
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  • DING Jinxi, HU Xueying, JI Na
    2015, 46(1): 107-112.
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