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    药物研究
  • 药物研究
    LUO Xiao-xiao;ZHAO Yi-lin;LI Shi-yong;TAN Lei;WANG Jin-tao
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    ObjectiveTo investigate the timedependent effects of ketamine on myocyte enhancer factor 2(MEF2)signaling pathway and expression of synaptogenesis synapsin I of rat developing hippocampal neurons in vivo.MethodsForty 5dayold rats were randomly divided into 4 treatment groups receiving ketamine (20 mg﹒kg-1)single injection and a control group receiving no treatment.Pups were killed by decapitation to extract total RNA from hippocampal neurons in the 4 treatment groups at 2, 4, 6,24 h, respectively, and from the control group.RealtimePCR was used to detect the expression of the MEF2 mRNA、synGAP I mRNA and Arc mRNA and synapsin I mRNA after intervention.ResultsCompared with the control group, there are significant decreases in the expression of MEF2 mRNA, synGAP I mRNA, Arc mRNA and increase in synapsin I mRNA of the neurons from ketamine treatment groups(P<0.05).ConclusionThe mechanism of ketamineinduced decrease in expression of MEF2 signaling pathway and increase in the expression of synapsin I may be related to decreased expression of Arc signaling pathway, which in turn regulates the expression of snapsin I in the developing hippocampal neurons.
  • 药物研究
    YU Jing;WANG Jian-xin;SU Su-wen;XIE Ke-rang;ZHANG Yu;YANG Ji-zhang;SU Yue
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    ObjectiveTo investigate the potential protective effect of extracts from Herba siegesbeckiae (HS) on hepatic and renal injury induced by doxorubicin(DOX) in rats.MethodsMale SpragueDawley rats were randomly divided into 4 groups with 10 in each.Rats in the low and high dose groups were intragastrically administered with HS extract at the doses of 170 and 340 mg﹒kg-1﹒d-1, respectively, for 7 consecutive days.Rats in the control and model groups were given with equal amount of water.On the 5th day, all groups were given with DOX (20 mg﹒kg-1) intraperitoneally except the control, which was given equal amount of saline.On the 7th day, evaluation of hepatic and renal protection effects by HS extract was performed by analyzing the serum biochemical indicators, contents of preoxidation(MDA), and free radicals in both serum and tissues of the liver and the kidneys.ResultsPretreatment with HS showed significant decrement of serum BUN、ALT and AST levels in a dosedependent manner compared with DOX group.The increment of MDA production and decrements of SOD and CAT caused by DOX were also recovered dose dependently in HS treated groups.The hepatic cells in the DOX group showed obvious congestion and swelling, whereas the symptoms in HS group were significantly relieved in a dose dependent manner.The renal interstitial in the DOX group showed obvious congestion and swelling, however the symptoms in HS group were significantly relieved.There was no obvious congestive swelling phenomenon in high dose of HS group.ConclusionHS has protective effect against DOXinduced hepatic and renal toxicities in rats which may be caused by its anti-oxidative effect.
  • 药物研究
    LI Xin-xin;YANG Xiu-li;CHEN Xiao-lei;HAO Wei;WANG Yi-ran
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    ObjectiveTo study the intervention and protective effect of Caspase3 inhibitor on damaged brain tissues of methamphetamine dependent rats.MethodsThe chronic methamphetaminedependent rat model was established.Caspase-3 inhibitor (z-DEVD-fmk) was injected into lateral ventricles to determine the changes of NO, SOD and MDA of the hippocampus in the rats.ResultsNO and MDA were significantly increased, and SOD decreased in the hippocampus of the chronic methamphetamine dependent rats.NO and MDA were slightly increased and SOD slightly decreased in the MA+z-DEVD-fmk plus methamphetaminedependent rats.There was significant difference between the two groups (P<0.01).ConclusionThe caspase-3 inhibitor can reduce the expression of NO and MDA, and increase the expression of SOD in the hippocampus of the chronic methamphetamine dependent rats.The caspase-3 inhibitor exerts protective effect on rat brain.
  • 药物研究
    SONG Zhao-hua;ZHU Bao-an
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    ObjectiveTo observe the protective effect and mechanism of the total flavonoids of verbena on rats with septic acute lung injury (ALI).MethodsA total of 120 rats were randomly divided into sham operation group (0.9% sodium chloride solution), model group (0.9% sodium chloride solution), dexamethasone positive control group (2.0 mg﹒kg-1, ip), low, middle and high dose of the total flavonoids of verbena group (50.0, 100.0, 150.0 mg﹒kg-1, ip).Rat model with ALI was induced by Cecal ligation and puncture (CLP).The rats were injected with physiological saline, dexamethasone, low, middle and high dose of the total flavonoids of verbena, respectively 24 h after establishment of the ALI model, and executed 48 h later.Bronchoalveolar lavage fluid (BALF) changes in leukocyte, protein content and the lung tissue wet to dry weight ratio (W/D) were observed, and the levels of inflammatory mediators, oxidation stress and nuclear transcription factor (NF-κB) p65 expression and cell apoptosis in lung tissue were compared.ResultsTotal flavonoids of verbena significantly decreased leukocytes, protein content and W/D in BALF (P<0.05 or P<0.01), decreased microphage inflammation protein-2 (MIP-2), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) and apoptotic rate of lung cells and expression of NF-κB p65 (P<0.05 or P<0.01), and improved MDA content, activity of superoxide dismutase (SOD) and myeloperoxidase (MPO) (P<0.05 or P<0.01).The effects were the greatest in the high dose group (P<0.01).ConclusionThe total flavone of verbena can reduce the levels of inflammatory mediators, reduce lipid peroxidation, improve the alveolar capillary permeability, and alleviate the occurrence and development of ALI.
  • 药物研究
    QI Mi-xia;NING Hua-lan;YANG Yan-fang;LV Li-ya;HE Jing-bo
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    ObjectiveTo study the effect of xiaochaihu decoction on type 2 diabetes and its underlying mechanism.MethodsType 2 diabetic mice was induced by highfatdiet and a single intraperitoneal injection of streptozotocin.The mice were orally given rosiglitazone, low, middle or high dose of xiaochaihu decoction, or 0.9% sodium chloride solution, separately.Blood glucose was detected every week.After treatment for four weeks, oral glucose tolerance test (OGTT) was determined.Serum insulin, total cholesterol (TC), triglyceride (TG), highdensity lipoprotein (HDL), and low density lipoprotein (LDL) were tested after treatment for six weeks.Expression of peroxisome proliferatoractivated receptor γ (PPARγ)and glucose transporter 4 (Glut4) in adipose tissue was investigated by Western blotting.ResultsXiaochaihu decoction significantly increased blood glucose and decreased serum insulin levels, and improved OGTT in type 2 diabetic mice.Treatment of xiaochaihu decoction also exhibited lower LDL, higher HDL, but not improving TC and TG.Expression of PPARγ and Glut4 in the adipose tissue was higher after xiaochaihu decoction treatment.ConclusionXiaochaihu decoction has hypoglycemic and hypolipidemic effects in type 2 diabetic mice, which may be related to the higher expression of PPARγ and Glut4 in adipose tissue, and enhanced insulin sensitivity in peripheral tissues.
  • 药物研究
    ZHU Fang-qing;CHEN Wei-guo;CHEN Jie;LIN Hao;LIU Li-xi;GONG Min;WEN Ping;WEN Jian-bo
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    ObjectiveTo investigate the effect of oxymatrine on enterogenous endotoxemia in rats with cirrhosis.MethodsThirty rats with carbon tetrachloride (CCl4)induced cirrhosis were randomly divided into two groups:the treatment group, who received oxymatrine intramuscular injection (63 mg﹒kg-1);and the model control group, who received the same volume of 5% glucose solution.Another 10 healthy rats served as the normal control group.At the end of the experiment, serum samples were taken from the portal vein for the detection of endotoxin level with a Kinetic Turbidimetric Limulus Amebocyte Lysate Kit.Concentration of TNF-α and IL-6 in the ileum tissue was analyzed by enzymelinked immunosorbent assay (ELISA).A piece of terminal ileum was also sampled for histopathologic examination.ResultsThe serum endotoxin level was significantly elevated in the model control group than the normal control group.After the treatment with oxymatrine, the serum endotoxin level was significantly decreased compared with the model control (P<0.01).Administration of oxymatrine resulted in a significant reduction in the concentration of TNF-α and IL-6 compared with the model control group (P<0.01).The intestinal mucosal villi in rats of the model control group were atrophic, shorter, fractured, and infiltrated with inflammatory cells into the lamina propria and even muscular layer.The swelling of the villi was serious and structure of mucous membrane became loose.This observation was reversed in the treatment group.ConclusionOxymatrine decreased enterogenous endotoxemia in cirrhotic rats by reducing the concentration of TNF-α and IL-6 and improving intestinal barrier function.
  • 药物研究
    HUANG Yan-feng;HE Xian-jiao;JIN Ling;ZHAO Shan-min;WANG Cai-bing;HUANG Yong-yi
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    ObjectiveTo observe the effect of Paris polyphylla water extract on gastrointestinal movement.MethodsBy using propulsion test, the effect of Paris polyphylla water extract (2.5 and 5.0 g﹒kg-1) on gastric emptying and intestine propulsion was studied in normal, neostigmine, atropine and adrenalinetreated mice.ResultsUnder normal circumstances, low dose of Paris polyphylla water extract promoted small intestine propulsion, while the high dose inhibited small intestine propulsion.Both low dose and high dose of the water extract inhibited gastric emptying of mice.The low dose of Paris polyphylla water extract antagonized atropine and adrenaline to promote intestine propulsion in the atropine and adrenaline treated mice, respectively;while the high dose had synergistic effect with atropine and adrenaline to inhibit gastric emptying of those mice.Both the low and high doses antagonized neostigmine to inhibit gastric emptying and intestine propulsion in the neostigminetreated mice.ConclusionThe effect of Paris polyphylla water extract on gastrointestinal movement may be related with M cholinergic receptor and adrenergic system.
  • 药物研究
    WU Qiong;MA Hong-da;SUN Xue-hui;HU Bei;JIA Hui;CHEN Yu-feng
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    ObjectiveTo study the analgesic effect of the water extract from Chrysanthemum indicum on mice.MethodsAlgogenic model of mice was induced by injection of capsaicine in the paws.Total time of pawslicking in 5 min after injection of capsaicin was observed from the mice.The analgesic effects of the extract were respectively observed by subplantar capsaicin injection and tailflick test.The openfield test and pentobarbital sodiuminduced sleeping time test were observed.ResultsGiven orally, the extract produced significant inhibition on chemical nociception induced by subplantar capsaicin injection and on thermal nociception in the tailflick test.In the pentobarbital sodiuminduced sleeping time test and the openfield test, the extract neither significantly enhanced the pentobarbital sodiuminduced sleeping time nor impaired the motor performance.ConclusionChrysanthemum indicum has analgesic effects that are unlikely related to sedation or motor abnormality.
  • 感染性疾病用药专栏
  • 感染性疾病用药专栏
    LIN Rong-fang;WANG Chang-lian;HUANG Pin-fang;LIN Li-dan
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    ObjectiveTo explore the factors predicting the response to the treatment of HBeAgpositive chronic hepatitis B (CHB) with Peginterferon alfa-2a (PEG-IFNα-2a).MethodsClinical efficiency of PEG-IFNα-2a in treating HBeAg (+) CHB patients for at least 48 weeks was retrospectively analyzed.The patients were divided into groups A and B according to the serological response.The ALT levels, HBV-DNA load, and HBeAg at the baseline and 4, 12 and 24 weeks after the treatment were compared.ResultsALT at the baseline was significantly higher in group A than in group B (P<0.01).After treatment for 4, 12, and 24 weeks, there was no difference in ALT between the two groups.There were significant differences in HBV-DNA load and its decrement between the two groups during different time of treatment (P<0.05).There were significant differences in HBeAg level and its decrement between the two groups after treatment for 12 and 24 weeks (P<0.01).Serological response rate was higher in patients with HBeAg decrement higher than 2log10.ConclusionBaseline ALT levels, HBV-DNA load and the decrement during the treatment, HBeAg levels and the decrement after treatment for 12 and 24 weeks are predictive for serological response after treatment with PEG-IFNα-2a for 48 weeks in CHB patients.
  • 感染性疾病用药专栏
    QIU Yue;ZOU Xiao-qin;HUANG Zhen-guang;WAN Rui-rong;LI Hui;LIU Tao-tao
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    ObjectiveTo investigate the antibiotic use and the pathogenic bacteria for infective endocarditis (IE).MethodsRetrospective study of 32 adults who were admitted to a tertiary hospital in 2012 with definite IE was conducted regarding predisposing cardiac factor, clinical presentation, etiology, echocardiography, inhospital course and clinical outcome.ResultsThe bacterial positive rate of the blood culture was 53.12% (n=17).There were 10 strains of streptococcus, 3 strains of enterococcus faecalis, 2 strains of candida parapsilosis, 1 strain of staphylococcus epidermidis and 1 strain of acinetobacter baumannii.Penicillin was the most frequently utilized antibiotics (n=23,71.9%).All streptococci were sensitive to penicillin.ConclusionStreptococcus is the major pathogen still.High dose penicillin, β-lactam/β-lactamase inhibitors and aminoglycosides are the main regimen in this study, consistent with the current treatment guidelines for IE.
  • 药物与临床
  • 药物与临床
    YIN Yi-ping;ZHOU Qin;LIU Xiao-fan;GUO Guang-yun;AI Lin
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    ObjectiveTo evaluate the clinical efficacy of different administration methods of glucocorticoid to the patients with chronic obstructive pulmonary disease (COPD) exacerbation.MethodsIn total, 62 cases with COPD were randomized into the oral treatment group (30 cases) and the intravenous therapy group (32 cases).In the oral treatment group, methylprednisolone of 32 mg was given orally daily for 7 days.In the intravenous therapy group, the patients were administrated with methylprednisolone via intravenous drip (1 mg﹒kg-1﹒d-1) in the first 3 days, followed by half of the dose in the next 4 days.Other treatments included oxygen therapy, antiinfection, administration of bronchodilators and expectorants as needed.The following indicators were examined before and after the treatment:forced expiratory volume in 1 second (FEV1), partial pressure of oxygen in arterial blood (PaO2), COPD assessment test TM (CAT), medicine research council scale (MMRC), length of hospital stay, combination of hyperglycemia and hypertension, and followup for 3 months after the patients were discharged from hospital.ResultsAfter the treatment, FEV1, PaO2, CAT and MMRC were significantly improved from the baseline in both groups (P<0.05), with no significant differences between the two groups.Incidence rates of hyperglycemia and hypertension were significantly higher in the intravenous therapy group than in the oral treatment group (P<0.05).In addition, the rate of relapse in 3 months after leaving the hospital was significantly higher in the intravenous therapy group than in the oral treatment group (P<0.05).ConclusionOral and intravenous administrations of glucocorticoid have the same curative effect on patients with COPD exacerbation.Oral administration is superior to intravenous injection for its fewer complications and relapse rate.
  • 药物与临床
    ZHAN Zhou-bing;SHI Yong-bing;FENG Sheng;WANG Yun;ZHAN Tian-jie;WANG Zhi;JIN Dong-hua;SHI Xiao-song;SHEN Hua-ying
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    ObjectiveTo observe the efficacy and safety of pramipexole on peritoneal dialysis patients with restless legs syndrome (RLS) and its possible adverse reactions.MethodsIn total, 22 peritoneal dialysis patients with RLS who were regular followed up in our peritoneal dialysis centre from January 2011 to January 2013 were selected and given pramipexole ranged from 0.125 to 0.5 mg﹒d-1 before sleeping for 6 weeks.Such efficacy evaluations as the international RLS study group scale (IRLS) and Pittsburgh Sleep Quality Index (PSQI) were adopted to assess severity of RSL and sleep quality.The results were analyzed statistically.The incidence rates of adverse events were recorded.ResultsThe scores of mean IRLS (17.69±1.84 vs.7.69±3.77 in moderate RLS, 26.20±3.03 vs.9.20±0.84 in severe RLS, 37.00±1.41 vs.11.50±0.71 in extremely severe RLS), total PSQI (12.81±1.50 vs.6.52±1.40), sleep quality (2.14±0.73 vs.1.10±0.70), sleep latency (2.38±0.59 vs.1.29±0.64), sleep duration (2.05±0.74 vs.0.95±0.67), sleep efficiency (1.95±0.81 vs.0.86±0.73), sleep disorders (2.10±0.77 vs.0.95±0.67), daytime function (2.19±0.68 vs.1.13±0.66) were significantly improved compared with those before the treatment (P<0.05).One patient had sleepiness and mental abnormalities after taking the medicine, which were alleviated after drug discontinuation.Nausea and stomach discomfort occurred in three patients and the symptoms disappeared after the withdrawal of pramipexole.ConclusionPramipexole can effectively control RLS of peritoneal dialysis patients and improve their condition.
  • 药物制剂与药品质量控制
  • 药物制剂与药品质量控制
    YUAN Yu-xia;GUAN Yan-bin;ZHOU Ning;WANG Jia-le;JIA Yong-yan
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    ObjectiveTo optimize the preparation process of compound levofloxacin in situ thermo sensitive gel.MethodsGelation temperature served as the indicator.Dosage of gel base Pluronic@F127 and temperature regulator Pluronic@F68, and the influence of drug on the gelation temperature were investigated.By using the star designresponse surface method, the prescription of compound levofloxacin temperature sensitive in situ gel type was optimized.ResultsIn a certain concentration range, the gelation temperature reduced gradually with the increased dose of Pluronic@F127 and decreased dose of Pluronic@F68.The optimal prescription was as follows:Pluronic@F127 192.7 g, Pluronic@F68 93.1 g, water added to 1 000 mL.ConclusionThe optimized prescription process is stable and feasible.The prepared compound in situ thermo sensitive gel with levofloxacin is viscous liquid at room temperature, but immobile at body temperature.The prepared gel meets the quality requirements.
  • 药物制剂与药品质量控制
    LU Yuan-yuan;FU Xu-dong;HU Dai;ZHAO Qian;LI Xue-mei;
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    ObjectiveTo establish a simple and accurate method to evaluate the release behavior of thermo sensitive liposome (TSL).MethodsCalcein thermo sensitive liposome (CTSL) was prepared by film hydration method, and the release behavior was measured by fluorescence quenching method.Then the transformation temperture was verified by differential scanning calorimetry.ResultsThermo sensitive liposome with different phospholipids could encapsulate the high concentration of calcein successfully, and trapped calcein could shield its emitted light.Calcein was in a good linearity among the concentrations of 10-4~10-3 mmol﹒L-1.The 10min release rate at 37 and 41 ℃ were 0.1% and 45.4%, respectively.The transformation temperature of CTSL was 41 ℃.ConclusionThe simple and accurate method to evaluate thermo sensitive liposome release behavior is successfully established based on fluorescence quenching method.
  • 药物制剂与药品质量控制
    CHEN Qin-hua;XIONG Lin;LI Peng;ZHU Jun
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    ObjectiveTo develop a new method of GC-MS assay for the determination of isoimperatorin in Angelica dahurica.MethodsIsoimperatorin was analyzed quantitatively on the DB-5MS quartz capillary chromatographic column by elective ion monitoring.The sample was extracted by ultrasound in acetic ether.ResultsThere was a good linear relationship in the range of 1.33-133.00 μg﹒mL-1(r=0.998 6) in isoimperatorin.The average recovery was 100.3% and the detection limit was 0.1 ng•mL-1.ConclusionThe method is convenient, of good sensitivity and accuracy.It can be used to determinate the content of isoimperatorin in Angelica dahurica.
  • 药物制剂与药品质量控制
    WANG Hai-bo;DENG Ming;ZHU Jian-ping;ZHU Rong;CHEN Ning-zhou;ZHU Bin
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    ObjectiveNIR method was developed for rapid determination of content of cefixime granules.MethodsThe diffuse reflectance near-infrared spectra of cefixime granules from different pharmaceutical factories in China were determined by a fiber optic probe.For quantitative analysis, the first derivative combining vector normalization method was used for pretreatment of the spectra, the wavelength rang of 4 597.5-6 101.7 cm-1 was selected to set up the calibration curve by the Partial Least squares Regression(PLSR)method.ResultsFor the quantitative model, 77 batches were used as calibration set, and 30 batches as validation set, the concentration range was 2.4%-5.2%, and the correlation coefficient of cross validation was 0.970 7, the RMSECV was 0.142%, and the RSD was less than 5%.ConclusionThe method is simple, rapid, and can be applied for rapid determination of the content of Cefixime granules.
  • 药物制剂与药品质量控制
    WANG Ya-jing;DENG Hong;ZHANG Shu;HUANG Xue-feng
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    ObjectiveTo establish a method for the determination of the content of benazepril hydrochloride and amlodipine besylate capsules.MethodsUltra performance liquid chromatography (UPLC) was adopted in this study.The analytical column was BEH C18 (100 mm×2.1 mm, 1.7 μm) and the mobile phase was methanolwaterformic acid (65:35:1 in volume) at a flow rate of 0.2 mL﹒minL-1.The ultraviolet (UV) detection wavelength was 240 nm, the column temperature was 30 ℃, and the injection volume was 2 μL.ResultsAmlodipine besylate could be well separated from Benazepril hydrochloride under the conditions mentioned above.The linear relationship between the concentration and area of chromatographic peak were established in the range of 5.14-51.40 μg﹒mL-1 for amlodipine besylate and in the range of 19.92-199.24 μg﹒mL-1 for benazepril hydrochloride(r=0.999 9).The average recoveries of amlodipine besylate and benazepril hydrochloride were 100.3% and 99.3% (n=9), respectively.ConclusionThe method is simple, specific, accurate and suitable for the determination of the content of amlodipine besylate and benazepril hydrochloride capsules.
  • 药物制剂与药品质量控制
    MA Ai-ling;ZHANG Hai-feng;DONG Ling-fang;WANG Yi-meng;LIU Sheng-qun
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    ObjectiveTo establish an high performance liquid chromatography (HPLC) method for content determination of propofol in propofol injection.MethodsThe analysis was performed on an Agilent TC-C18 (250 mm×4.6 mm, 5 μm) column.The mobile phase consisted of methanolwater (80:20), with a flow rate of 1.0 mL﹒min-1, and detection wavelength at 271 nm.ResultsThere was a good linear relationship for propofol in the range of 25-250 μg﹒mL-1.The average recovery rate was 97.26% and the RSD was 1.38%.ConclusionThis method is simple, sensitive and accurate, and it can be used for determination of propofol injection.
  • 药物制剂与药品质量控制
    REN Han-cheng;ZHAO Hai-long
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    ObjectiveTo establish a high performance liquid chromatography (HPLC) method for determination of the related substances of atorvastatin intermediate L1.MethodsThe chromatographic separation was performed on Agilent Poroshell EC-C18 column (100 mm×4.6 mm, 2.7μm) with the mobile phase consisting of H2O:ACN:THF:MeOH (36:8.4:29:26.6).The flow rate was 0.7 mL﹒min-1, the detection wavelength was 246 nm, and the column temperature was 30 ℃.ResultsThe method achieved good separation between L1 and its related impurites including L1 defluorination, L1-R,S, and L1 diamination.The linear range was 0.124 1-1.488 0 μg﹒mL-1 (R2=0.999 5, n=7), 0.386 6-3.093 0 μg﹒mL-1 (R2=1, n=6), 0.357 1-2.856 0 μg﹒mL-1 (R2=0.999 0, n=6), and 0.187 3-1.498 0 μg﹒mL-1 (R2=0.999 3,n=6) for L1 diamination, L1 defluorination, L1-R,S, and L1 difluorination, respectively.The specifications of each impurity all reached the LOQ.ConclusionL1 separates well with the impurities.The method is accurate and reliable.