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OBJECTIVE To establish the method for content determination of related substances in Oxcarbazepine tablets. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted and the separation was performed on ZORBAX Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate solution （pH6.0） （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was 230 nm and column temperature was set at 35 ℃. The sample size was 10 μL. RESULTS The linear ranges of oxcarbazepine and impurity A， B， C， D， E， I， K， L and N were 0.192-1.440， 1.019-7.639， 0.208-1.559， 0.230-1.727， 0.389-2.915， 0.182-1.364， 0.393-2.945， 0.199-1.493， 0.199-1.490 and 0.200- 1.503 μg/mL， respectively （all r＞0.999）. The detection limits were 0.046， 0.037， 0.049， 0.027， 0.077， 0.040， 0.114， 0.054， 0.055 and 0.039 μg/mL. The quantitation limits were 0.152， 0.122， 0.162， 0.090， 0.258， 0.132， 0.380， 0.181， 0.185 and 0.130 μg/mL. RSDs of precision， repeatability， stability （24 h） and durability tests were all lower than 5.0%. The average recoveries were 92.8%-105.6% （RSD≤3.0%， n＝9）. Only impurity K and unknown impurity were detected in the original preparation sample， with a total content of 0.078% to 0.083%； impurities A， B， D， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅰ， with a total content of 0.147% to 0.163%； impurities A， B， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅱ， with a total content of 0.085% to 0.161%. CONCLUSIONS The established method is rapid， sensitive， accurate， stable and durable. It can be used for the content determination of 9 known impurities in Oxcarbazepine tablets.
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OBJECTIVE To establish a method for the simultaneous determination of 10 rhubarb anthraquinones in Compound gentian sodium bicarbonate tablets and the content of rhaponticin，which are the characteristic components of artifacts，and to use the method to evaluate the quality of compound preparation containing Rheum officinale. METHODS The ultra-performance liquid chromatography （UPLC） method was adopted to determine the contents of 10 rhubarb anthraquinones （aloe-emodin-8-O-glucoside， rheinic acid-8-O-β-D-glucoside，emodin-8-O-glucoside，chrysophanol-8-O-β-D-glucoside，emodin monomethyl ether-8-O-β-D-glucoside， aloe-emodin，rheinic acid，emodin，chrysophanol，emodin monomethyl ether） and rhaponticin in 40 batches of Compound gentian sodium bicarbonate tablets from 8 manufacturers. The determination was performed on the Agilent Eclipse Plus C18 column with a mobile phase consisted of acetonitrile-0.1% phosphoric acid solution （gradient elution） at a flow rate of 0.3 mL/min； the column temperature was set at 30 ℃ ，and the injection volume was 5 μL. Combining principal component analysis and cluster analysis to synthesize the results of content determination，the quality of samples from different manufacturers was evaluated. RESULTS All of above 11 components showed favorable linear relationships with peak areas in their respective mass concentration ranges （r≥0.999 3），with RSDs of precision，repeatability and stability 296261547@qq.com less than 3% （n＝6）； average sample recoveries ranged 96.82%-98.92% （RSD≤1.74%，n＝6）； their contents were 0971-8247794。E-mail：304436784@qq.com 0.011 7-0.252 0，0-0.323 3，0.131 3-1.236 6，0.081 1-1.056 2，0.015 2-0.189 8，0.001 8-0.152 3，0-0.255 2，0.001 9-0.223 4，0.054 3-0.303 0，0.022 7-0.172 2，0-2.835 9 mg/g，respectively. The cumulative variance contribution of the first three principal components was 95.533%； the 40 batches of samples can be clustered into 4 categories：samples from enterprises a and d were in a category of their own，samples from enterprises f，b，g and e were in a category，and samples from enterprises c and h were in a category. There were large differences in the content of rhubarb anthraquinone in the samples from 8 manufacturers，and rhaponticin was only detected in the sample from one enterprise. CONCLUSIONS Established UPLC method is stable and reliable； it can be used for the content determination of 10 rhubarb anthraquinones and rhaponticin in Compound gentian sodium bicarbonate tablets.
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OBJECTIVE：To es tablish a method for the content determination of heavy metals [lead （Pb），cadmium（Cd）， copper （Cu）， mercury （Hg）] and harmful elements [arsenic （As）] in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules. METHODS ：The samples were conducted pretreatment by microwave digestion instrument and determined by inductively coupled plasma mass spectrometry （ICP-MS）using elements germanium ，indium，bismuth as internal standard. RESULTS ：The linear ranges of Pb ，As，Cu，Cd and Hg were 1-20，0.5-10，5-100，0.5-10 and 0.2-4 ng/mL， respectively （all r＞0.997）. The limits of detection （LODs） were 0.041 1，0.013 2，0.057 3，0.009 0，0.005 4 ng/mL， respectively. The limits of quantification （LOQs）were 0.137 0，0.044 0，0.191 0，0.030 0，0.018 0 ng/mL，respectively. RSDs of precision and repeatability tests were all less than 6％. RSDs of stability tests （28 h）of Pb ，As，Cu and Cd were all less than 5％， and that of stability test （28 h）of Hg was less than 7％. The average recoveries were 89.44％（RSD＝5.87％，n＝9），99.56％ （RSD＝5.46％ ，n＝9），96.12％（RSD＝4.62％ ，n＝9），105.82％（RSD＝2.80％ ，n＝9）and 90.23％（RSD＝3.59％ ，n＝9）， respectively. Five elements were all detected in 63 batches of samples ，and the contents of them were 0.191 0-1.527 6，0.002 5- 0.047 4，0.034 1-1.549 0，0.001 5-0.078 8 and 0.001 9-0.005 4 mg/kg，respectively. CONCLUSIONS ：The method is simple ， sensitive and accurate. It is suitable for simultaneous determination of 5 elements in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules.
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OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.
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Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2％ rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.
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OBJECTIVE： To establish a method for qualitative screening and quantitative determination of indicative composition rhaponiticin from counterfeit Rheum palmatum in Compound gentian and sodium bicarbonate tablets. METHODS： Totally 45 batches of Compound gentian and sodium bicarbonate tablets were collected from 8 domestic pharmaceutical manufacurers （No. A-H） in the field of drug distribution. TLC method was used to identify rhaponiticin in the samples primarily. The content of rhaponiticin was determined by HPLC， and then UPLC-MS/MS method was used to confirm the structure of rhaponiticin. RESULTS： TLC results showed that bright blue fluorescent spots of rhaponiticin could be seen in 10 batches of samples from manufacturer D at 365 nm wavelength of ultraviolet lamp. Results of HPLC methodology investigation showed that the linear range of rhaponiticin was 0.884-88.4 μg/mL（r＝0.999 9）； the detection limit and quantitative limit were 0.707 2， 3.536 ng； RSDs of precision， reproducibility and stability tests were all lower than 1％； average recovery was 96.55％ （RSD＝0.53％，n＝6）. The contents of rhaponiticin in 10 batches of samples from manufacturer D were 0.732 4-2.890 8 mg/g. Results of UPLC-MS/MS method showed that quasimolecular ions with m/z of 419.0 and fragment ions with m/z 257.1 and 241.2 were found in both samples from manufacturer D and rhaponiticin control. CONCLUSIONS： TLC for primary screening， HPLC for content determination and UPLC-MS/MS for structure confirmation is simple， sensitive and reliable， and can be used for qualitative screening and quantitative determination of rhaponiticin in Compound gentian and sodium bicarbonate tablets. Among 45 batches of samples tested， rhaponiticin is detected in 10 batches of samples from one manufacturer， suggesting that the manufacturer substitute fake R. palmatum for genuine ones in the production of Compound gentian sodium bicarbonate tablets.
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OBJECTIVE:To establish quality standard for Jingbi mixture. METHODS:TLC was adopted to identify the Notop-terygii Rhizoma et Radix,Aucklandia lappa and Pueraria lobata and determine the relative density and pH according to pharmaco-poeia method. HPLC was adopted to determine the content of puerarin. Column was XTerra? RP18 with mobile phase of acetoni-trile-0.05% phosphoric(10:90,V/V)at flow rate of 1.0 ml/min,detection wavelength was 250 nm,column temperature was 25 ℃and volume injection was 10 μl. RESULTS:TLC of Notopterygii Rhizoma et Radix,A. lappa and P. lobata showed clear spots and good separation. The relative density was 1.08,and pH was 4.5. The linear range of puerarin was 2.079-33.26 μg/ml(r=0.999 8);RSDs of precision,reproducibility and stability tests were lower than 1.0%;recovery was 99.50%-100.50%(RSD=0.42%,n=6). CONCLUSION:The method is simple and good reproducibility,and can be used for the quality control of Jingbi mixture.
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Objective To investigate the significance of CD44v6 expression in acute leukemia( AL) and it's relation with the prognosis of AL. Methods Sixty AL patients were treated by enzyme linked immunosorbent assay( ELISA)as initial treatment group. Fourty-seven cases were remission as remission group, and 20 cases with no-remission group. Meanwhile,45 healthy people were served as the control group. The level of CD44v6 was measured by ELISA. Results The serum CD44v6 in initial treatment patients,remission group, no-remission group and control group were( 179. 34 ± 39. 41 )μg/L,( 190. 61 ± 28. 05 )μg/L,( 106. 72 ± 26. 38)μg/L and(98. 31 ± 21. 78)μg/L respectively,and the difference was significant( F =56. 303,P﹤0. 01),and the CD44v6 of initial treatment group and remission group were higher than that of no-remission group and control group(P﹤0. 05). The leukocyte levels was positive related to CD44v6 levels in 60 patients(r=0. 826,P﹤0. 01),and it was also related to disease stage,extramedullary infiltration(( r=0. 485,0. 512;P﹤0. 01). Conclusion The level of CD44v6 is closely related with the occurrence and development of acute leukemia. The assay of CD44v6 in serum of AL patients is helpful in diagnosing and predicting the risk of metastasis and prognosis in AL.
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The change in serum level of 8-hydroxy-deoxyguanosine (8-OHdG),an oxidative stress biomarker,in patients with active Graves' ophthalmopathy (GO) during corticosteroid treatment was observed.The serum level of 8-OHdG was significantly increased in patients with active GO as compared with that of normal controls and patients with Graves' disease (P ＜ 0.05).After systemic corticosteroid treatment,patients with GO showed significantly lowered 8-OHdG level as compared with that before treatment and patients with Graves' disease.These changes in serum 8-OHdG level were accompanied by decreases in clinical activity score (P ＜ 0.05) during corticosteroid treatment.Oxidative stress may play a role in the pathogenesis of GO.Serum 8-OHdG level may be used as an objective and quantitative parameter in patients with GO during immunosuppressive treatment.
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To investigate the role played by 8-hydroxy-deoxyguanosine (8-OHdG) in patients with Graves'ophthalmopathy(GO),and the association between 8-OHdG and the disease activity of GO.Serum levels of 8-OHdG were tested in 48 cases with GO and 30 cases with Graves' disease(GD) without ophthalmopathy.30 healthy subjects participated in this study as controls.8-OHdG was detected by enzyme-linked immunosorbent assay (ELISA).Compared with the controls,the mean level of 8-OHdG in GO patients and GD patients was increased significantly [(2.98±1.33),(2.07±1.30) vs(0.72±0.93)ng/ml,P＜0.05].Mean 8-OHdG level in GO patients was markedly higher when compared to GD patients(P＜0.05).Pearson regression analysis showed that elevated levels of 8-OHdG were significantly correlated with the Clinical Activity Score of GO (r =0.54,P＜0.01).The serum level of 8-OHdG in GO patients was raised obviously,it implies that oxidative stress plays an important role in the pathogenesis of GO,and the serum level of 8-OHdG might act as an activity index of GO.
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The standardization of data transfer plays an important role in precise radiotherapy,not only boosting the speed but also ensuring the treatment quality.In this article,a method for beam data generation and transfer is introduced based on DICOM RT Standard.Firstly,the realization procedure of this module is presented.Secondly,the realization means of two different IMRT methods including SMLC and DMLC are explained respectively.Finally,the system's validity is proved with instances.