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??OBJECTIVE To evaluate the effects of hormone replacement therapy(HRT) on the quality of life in climacteric women.METHODS The 202 patients were collected and divided into three groups according to whether or not they were treated with HRT: group 1 (not HRT), group 2 (HRT for the first time), group 3 (HRT for more than one year). All patients received follow-up visiting once per three months for one year. They were evaluated by the professionals through Kupperman index(KI), menopause-specific quality of life questionnaire(MENQOL), self-rating anxiety scale(SAS), self-rating depression scale(SDS). All patients were guided to improve the way of life.RESULTS After a year, KI, MENQOL and SAS in the three groups were improved significantly (P=0.003, 0.007, 0.014). KI and MENQOL were improved earlier than SAS. SDS was improved but not significantly(P=0.109). KI, MENQOL, SAS and SDS of patients in group 1 were improved significantly, but improved more weakly than those in group 2 and group 3. There is negative correlation between HRT and the values of every scale, and there is positive correlation between culture degree and SAS, SDS score values. CONCLUSION HRT canim prove the quality of life in climacteric women. The improvement in physical symptoms is earlier than that in mental symptoms. Anxiety and depression are more likely to occur in menopausal patients with high degree of education. Traditional Chinese medicine, exercise therapy and physical rehabilitation can be used as an auxiliary treatment for patients who are unable or unwilling to accept the HRT.     

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??OBJECTIVE To establish an RP-HPLC analytical method for simultaneous determination of crysoeriol and centaureidin in the aeries parts of Echinops integrifolius. METHODS The separation was achieved on a Kromasil C₁₈ column ( 4. 6 mm??250 mm,5 ??m)at 30 ?? using acetonitrile-water-acetic acid solution (35??65??2) as mobile phase at a flow rate of 1.0 mL??min^-1 and 350 nm as the detection wavelength. RESULTS The linear ranges of crysoeriol and centaureidin were 0.4-2.4 mg??L^-1(r=0.999 8), 0.6-2. 6 mg??L^-1 (r=0.999 9), respectively. The average recoveries (n=6) were 91.6% and 92.7%, and RSDs were 1.37% and 1.08% respectively. CONCLUSION The methodology validation shows that this method is accurate,simple and reliable,which is applicable for the simultaneous determination of two flavonols crysoeriol and centaureidin in the aeries parts of Echinops integrifolius.     

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??OBJECTIVE To analyze the regularity, clinical reactions and outcomes of the adverse reaction of sorafenib to provide reference for safe medication in clinical practice. METHODS The case reports of sorafenib ADR which were published at international medical academic periodicals during 2006-2016 were collected and analyzed statistically in respect of gender, age, disease informations, clinical manifestation and RESULTS of treatment. RESULTS A total of 93 adverse reactions were identified and included in the analysis, 22 cases were unexpected ADR. The ADR happened in male was more than in female, and the age of 61-80 was the most common population (45.16%). The ADR was mostly happened in 1 month (71.11%) after therapy. Lesions of skin and its appendants were the most commonly reported ADRs (51.52%), followed by the lesions of digestive system (22.73%) ,which reported the most of the death cases (n=19 , 6 death). The ADR correlation rate was high in these case reports. CONCLUSION Multiple organ systems are involved in the ADRs of sorafenib, amd careful clinical observation and symptomatic treatment in time are necessary.     

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??OBJECTIVE To prepare the total alkaloids of Strychni Semen(TASS)-total glucosides of Paeony(TGP) gel and study its in vitro transdermal absorption of two alkaloids(strychnine and brucine) after the combination of TASS and TGP. METHODS The excised abdominal skin of mice was used as the permeation model. Utilizing the modified Franz diffusion cell, the suitable receiving solution was elected to test the content of two alkaloids by HPLC, and thus the percutaneous rates and permeability coefficients were obtained. RESULTS 20% Ethanol-normal saline was taken as receiving solution. With combination use of TASS and TGP, the penetration quantities of strychnine and brucine in different (1:1,1:3,1:6) gels were felled by 22.7%,48.4%,69.1% and 5.93%,23.8%,80.7% after 24 h. And with the increase of compatibility proportion, infiltration rate and skin retention rate also gradually reduced. CONCLUSION The compatibility of TASS and TGP drug delivery can reduce the toxic ingredients through capacity, there is a “attenuated” effect, the best ratio is 1:6.     

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??OBJECTIVE To examine the in vitro release profile and in vivo retention of estradiol vaginal thermosensitive gel (E2-VTG).METHODS E2-VTISG was prepared by cold dissolving method.The dynamic membrane dialysis method and HPLC-fluorometric method were used to determine the in vitro release characteristic of the estradiol vaginal thermosensitive gel.CRi Maestro was applied to evaluate the retention of E2-VTG in ICR mice with IR820 as the fluorescent marker. RESULTS Estradiol could be released slowly from the thermosensitive gel and the release profile was fitted with Higuchi equation. It was speculated that estradiol was mainly released through diffusion.NIR imaging and fluorescence quantitative analysis showed that thermosensitive gel could reside in vagina for at least 8 h. CONCLUSION Estradiol thermosensitive gel can prolong the drug residence time in vagina and sustain the drug release rate.     

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??Quercetin could affect both the in vivo and in vitro transport of a variety of commonly used drugs by modulating the uptake transporter organic anion transporter polypeptides (OATPs), organic anion transporters (OATs), efflux transporter P-glycoprotein (P-gp), multidrug resistance-related protein (MRP) and breast cancer resistance protein (BCRP), respectively. Quercetin can regulate various drug transporters, thereby affecting other drugs in vivo process.     

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??OBJECTIVE To establish dose-related lung inflammatory injury in rats model with intratracheal atomization of lipopolysaccharide (lipopolysaccharides, LPS). METHODS Four groups of 4 rats were subjected to solvent or a single dose of LPS by intratracheal route using a IA-1B-2 inches-microsprayer. The male rats received 200 ??L solvent (control), LPS solutions (15, 5, 0.5 mg??kg^-1). All rats were sacrificed 24 h after dose administration, biochemical analysis and cell counts on bronchoalveolar lavage fluid (BALF) were performed on each rat. Lung, trachea and kidney were examined histologically. Serum chemistry profiles of creatinine, ALB, Na, K, Cl^- were detected. RESULTS Cell counts in BALF showed LPS groups had different degrees of inflammatory reaction. The alkaline phosphatase and total protein concentration were higher in LPS high dose group compared with other groups. In addition, the concentration of TNF-?? increased consistently with LPS dose and has statistical significance compared with the control group. Histopathology findings demonstrated that LPS produced an accumulation of foamy macrophages in the lungs and high degree of inflammation. CONCLUSION The results recommends intratracheally atomizing doses of LPS in rats model produced ranks of lung inflammatory injury.     

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??OBJECTIVE To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t_1/2 were (347.33??9.32) and (390.82??8.78) min, t_max were (30.00??5.94) and (60.00??3.48) min, ??_max were (1 940.14??21.21) and (1 818.22??23.64) ng??mL^-1, AUC_0-t were (427 515.71??37 350.03) and (426 406.31??20 577.75) ng??min??mL^-1, AUC_0-inf were (545 423.14??47 969.18) and (593 569.87??30 247.35) ng??min??mL^-1, Vz/F were (43.48??4.75) and (44.96??3.81) kg??L^-1, CL/F were (86.78??3.35) and (79.74??2.89) kg??L^-1??min^-1, respectively. CONCLUSION Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t_1/2, lower ??_max and delayed t_max in rats.     

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??To improve the in vitro dissolution and in vivo absorption as well as the bioavailability after oral administration by increasing the solubility with the formation of solid dispersion remains a great challenge for the oral dosage form design of poorly water-soluble drugs. Compared with the other pharmaceutical techniques in improving the solubility for poorly water-soluble drugs, priorities are usually given to solid dispersion for its manufacturing convenience. Following the characteristics introduction, we were focused this review on the novel carriers and advanced techniques used for preparing solid dispersions. Amphiphilic polymers used as novel solid dispersion carriers are Solutol HS 15, Soluplus and poly [MPC-co-BMA]. Inorganic materials like magnesium aluminum metasilicat, mesoporous silica microparticle and mesoporous magnesium carbonate are introduced together with the advanced solid dispersing techniques such as supercritical fluid technology, high speed electro-spinning and microenvironmental pH modified technology.     

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??OBJECTIVE To investigate the chemical constituents of the seeds of Lepidium apetalum Willd. METHODS The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, MCI Gel CHP-20, ODS, silica gel chromatography combined with Pre-HPLC and the structures were identified on the basis of spectral data and physiochemical properties. RESULTS Sixteen compounds were isolated and identified from the water extract as catechol(1), protocatechuic aldehyde(2), 2-phenyl acetamide(3), methyl- 5-hydroxypyridine-2-carboxlate(4), benzylcarbamic acid(5), N-benzylacetamide(6), raphanuside C(7), 1-phenyl-1,2-ethanediol(8), 2-(4-hydroxyphenyl)-ethanol(9), isorhamnetin-7-O-??-L-rhamnopyranoside(10), kaempferol(11), methyl 2,4,6-trihydroxybenzoate(12), 2-(4-hydroxyphenyl)acetonitrile(13), syringic acid(14), protocatechuic acid(15), and methyl sinapate(16). CONCLUSION Compounds 1-16 are isolated from this plant for the first time.     

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??OBJECTIVE To establish a ¹H-NMR internal standard method for measurement of glucosamine hydrochloride in glucosamine hydrochloride capsules.METHODS For the HPLC-UV method, a China national drug tentative standard (No. YBH11442006) was employed. For the ¹H-NMR analysis, the optimal determination conditions were selected as followsthe pulse sequence was zgpr, hydrogen spectral width was 6 009 Hz, pulse width was 11.95 ??s, delay time was 6.50 ??s, the temperature was 27 ?? and the number of scans was 32.RESULTS The peak of ?? 3.05 ppm of the glucosamine hydrochloride and the peak of ?? 0 ppm of TSP were selected as quantitative peak and internal standard peak,respectively, and the concentration of the internal standard TSP was 1.02 mmol??L^-1. A good linear relationship was obtained with a regression equation as Y=2.717 7X+0.149 9(r=0.999 8) in the concentration range of 2.0-12.0 mg??mL^-1. The average recovery rate and the RSD of glucosamine hydrochloride capsules were 103.59% and 1.09% (n=9), respectively.CONCLUSION With simple pretreatment, high sensitivity, good repeatability and short analysis time, the NMR-based method could be applied to the measurement of glucosamine hydrochloride in glucosamine hydrochloride capsules.     

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??OBJECTIVE To develop a gradient supercritical fluid chromatography method for the separation of cinnarizine and its four related substances. METHODS Cinnarizine and its four related substances were separated on a Torus DIOL column (3.0 mm??100 mm,1.7 ??m) maintained at 40 ?? with the mobile phase consisting of CO₂ and methanol with 0.1% TFA-0.1% TEA at 1.5 mL??min^-1, the detection wavelength was set at 230 nm and the back pressure was set at 1.38??10⁷ Pa. RESULTS Cinnarizine and its four related substances were separated in 4.5 min with satisfying resolutions. Good linear relationships were established between the peak response and the concentration in the range of 2-20 ??g??mL^-1 for each related substance (r>0.999 9) and the detection limits were 0.7-1.3 ng(S/N??3). Good linear relationships were established between the peak response and the concentration in the range of 0.05-1.0 ??g??mL^-1 for cinnarizine (r=1.000 0). The spiked recovery of four related substances of cinnarizine was 98.0%-106.7%, and the RSD was 2.57%-4.44%(n=9). CONCLUSION The established method can be applied in the simultaneous determination of the related substances of cinnarizine and provide reference for the quality control.     

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??OBJECTIVE To develop an high-performance liquid chromatography (HPLC) method with diode array detector (DAD) for determination of acarbose in acarbose tablets. METHODS An Alltima C₁₈ column (4.6 mm??250 mm,5 ??m) was used for the separation, with acetonitrile-10 mmol??L^-1 ammonium dihydrogen phosphate (containing 0.04% sodium 1-octanesulfonate, adjusted pH to 3.3 with H₃PO₄) (15??85) as the mobile phase at the flow rate of 0.8 mL??min^-1. The detection wavelength was set at 200 nm and the column temperature was maintained at 30 ??. RESULTS The method showed good linearity with a correlation coefficients (r) of 1.000 0. The specificity study demonstrated satisfactory resolutions between acarbose, other ingredients in the drug and forced degradation products. The precision and stability were satisfactory with the relative standard deviations (RSDs) of 0.088% and 0.22%, respectively. The average spiked recovery was 98.49% with RSD of 0.24% (n=9). The content of acarbose in four batches of acarbose tablets was 51.69, 51.75, 51.72 and 51.62 mg??tablet^-1, respectively. CONCLUSION The established method is accurate, simple and rapid, and can be utilized for determination of acarbose in acarbose tablets.     

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??OBJECTIVE To establish an HPLC-ELSD method for determination of mesaconine.METHODS Gemini C₁₈ 110A column (4.6 mm??150 mm,5 ??m) was adopted with the mobile phase consisting of methanol-0.1%TFA (25:75) at the flow rate of 0.6 mL??min^-1. The detector was Alltech ELSD 2000ES, with the drift tube temperature of 90 ?? and the airflow velocity of 2.3 L??min^-1. RESULTS Under this conditions, mesaconine and the related substances were well separated. The linear range of mesaconine was 0.40-0.60 mg??mL^-1 (r=0.999 6). RSD of injection precision and repeatability test were 0.04% (n=5) and 0.7% (n=6), the intra day and inter day precision RSD were 0.4% and 0.6%, respectively. The average recovery was 101.0% (RSD=1.1%, n=9). CONCLUSION The established method was specific, simple, accurate, and suitable for determination of mesaconine.     

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??OBJECTIVE To develop an HPLC-ELSD method for determination of MPEG-DSPE and HSPC in doxorubicin hydrochloride liposome injection. METHODS The column was Waters Symmetry 300 C₁₈(4.6 mm??150 mm, 5 ??m;pore size:300). The mobile phase was methonal-tetrahydrofuran-0.17 mol??L^-1 ammonium acetate(93??6??1). The flow rate was 1.0 mL??min^-1. The column temperature was 25 ?? and the injection volume was 10 ??L. The ELSD conditions were as follows: Alltech 2000ES ELSD detector; drift temperature: 110 ??; rate: 2.6 L??min^-1. RESULTS This method had good specificity. The linear ranges of the calibration curves for MPEG-DSPE and HSPC were 0.03-0.48 mg??mL^-1 (r=0.999 8) and 0.1-1.0 mg??mL^-1 (r = 0.999 8), respectively. The average recovery rates of MPEG-DSPE and HSPC were 100.0% (n=3??3) and 101.0% (n=3??3), respectively. The LODs of MPEG-DSPE and HSPC were 13 and 52 ng, respectively. The repeatability and intermediate precision of MPEG-DSPE were 0.9% (n=5) and ??1.9%(n=3), respectively. The repeatability and intermediate precision of HSPC were 1.1%(n=5) and ??1.3%(n=3) , respectively. CONCLUSION The established method is accurate, reliable, repeatable and suitable for the determination of MPEG-DSPE and HSPC in doxorubicin hydrochloride liposome injection.     

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??OBJECTIVE To establish an RP-HPLC method for determination of the contents of eplerenone and its related substances. METHODS A RP-HPLC method was developed by using a C₁₈ column (Agilent Poroshell,4.6 mm??100 mm, 2.7 ??m), the mobile phase consisted of H₂O-CH₃CN-MeOH (64??18??18), the flow rate was 1.0 mL??min^-1, and the detection wavelength was set at 240 nm. The diluent was H₂O-CH₃CN-MeOH (50??25??25). RESULTS Eplerenone was well separated from the impurities. For the determination of related substances, the LODs of eplerenone, its intermediate (?? and ??) and related substances (A-E) were 0.03, 0.13, 0.25, 0.05, 0.05, 0.26, 0.07 and 0.12 ng, and the LOQs were 0.12, 0.42, 0.84, 0.18, 0.18, 0.86, 0.22 and 0.41 ng, respectively. The calibration curves of eplerenone and related substances (A-E) had good linear relationship within 0.13-1.53, 0.25-3.03, 0.25-2.99, 0.13-1.61, 0.14-1.63, and 0.13-1.54 ??g??mL^-1(r=0.999 9, n=7), and the correction factors of the related substances (A-E) were all in the range of 0.90-1.10. The average recoveries of the related substances (A-E) were all within 95.0%-105.0% (n=9). For the content determination of eplerenone, the validation test showed good linearity over the range of 12.60-75.63 ??g??mL^-1 (r=0.999 6, n=6) with good repeatability (RSD=0.19%, n=6). CONCLUSION The developed method proves to be simple, accurate, specific and reliable. It can be applied to the determination of eplerenone and its related substances.     

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??OBJECTIVE To establish an HPLC-PAD method to determine the related substances of sisomicin sulfate injection and compare with the statutory method. METHODS IonPac AMG C₁₈(4.0 mm??150 mm, 3 ??m)chromatographic column was used with acetonitrile-0.1 mol??L^-1 trifluoroacetic acid (containing 0.025% of pentafluoropropionic acid, 5 mL of 50% NaOH solution without carbonate, pH of the aqueous solution adjusted to 2.3 with 50% NaOH solution.)as mobile phase at a flow rate of 0.7 mL??min^-1. NaOH solution of 0.76 mol??L^-1 was added post column at a flow rate of 0.35 mL??min^-1. The column temperature was maintaine at 30 ??. PAD detector was operated with the cell temperature set at 35 ??. The working electrode was a gold electrode (diameter of 3 mm)and a quadruple-potential waveform was selected as detection waveform. The reference electrode was Ag/AgCl, the detection potential was four potential. The determination result of the related substances of sisomicin sulfate injection was compared with that of the statutory method. RESULTS The peaks of sisomicin sulfate, gentamicin C_1a and netilmicin could be completely separated, and other impurities could also be effectively separated. The blank sample had no interferences. The LOD and LOQ of etimicin were found to be 2 and 6 ng respectively, and the RSD of precision test (n=6) was 0.9%. Paired-samples t-test showed significance levels of P=0.034, P=0.364 and P=0.605 for total amount of impurities (%), the biggest single impurity (%)and content (%)respectively between the statutory method and the method of HPLC-PAD. CONCLUSION Compared with the statutory method, this HPLC-PAD method shows higher sensitivity, and is accurate and reliable. It can be applied to the determination of related substances in sisomicin sulfate injection.     

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??OBJECTIVE To establish a high performance size exclusion chromatography(HPSEC) method for the separation and analysis of polymers in cefotaxime sodium and cefotaxime sodium for injection, and determine the structures of the impurities by LC-MS. METHODS HPSEC was performed by using Sepax SRT SEC-150(7.8 mm??300 mm, 5 ??m)column. The mobile phase was 0.1 mol??L^-1 disodium hydrogen phosphate and 0.1 mol??L^-1 phosphate buffer solution. The flow rate was 0.8 mL??min^-1, the detection wavelength was set at 235 nm, the injection volume was 10 ??L, and the column temperature was maintained at 35 ??. The concentration of polymers was quantified by external standard method. The LC-MS/MSⁿ system conditions were as following: the mobile phase was 20 mmol??L^-1 amonium acetate, the flow rate was 0.8 mL??min^-1, ESI source with positive and negative ion scan was utilized, the scanning range was m/z 200-1 600, and the post-column diversion ratio was 1??4. RESULTS Eight impurity peaks were obtained in total; the resolutions were all greater than 1.5. The linear range of cefotaxime was 1-100 ??g??mL^-1(r=1.000 0). The RSD repeatability was 1.2%(n=6). The limit of detection was 0.2 ??g and the limit of quantitation was 0.4 ??g. Three polymers were identified by LC-MS. CONCLUSION The HPSEC method can be used for the quantitative and qualitative analyses of individual polymer impurities. It is also sensitive for the control of polymers in cefotaxime.     

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??OBJECTIVE To establish an HPLC-MS method for the analysis of the impurity profile of cefotaxime sodium. METHODS Shimadzu-LCMS-IT-TOF was used with Waters XBridge Shield (RP18,4.6 mm??250 mm, 5 ??m) column. Mobile phase A was 20 mmol??L^-1 ammonium acetate (pH adjusted to 6.25)-methanol (92:8), and mobile phase B was set at 20 mmol??L^-1 ammonium acetate-methanol (60:40) (pH adjusted to 6.25).Gradient elution was performed at a flow rate of 1.0 mL??min^-1. ESI source was used.Positive and negative ion scanning was conducted in the range of m/z 150-900.The heating temperature was 200 ??, CDL temperature was maintained at 200 ??, atomization gas flow rate was 1.5 L??min^-1, dry gas pressure was 94.0 kPa, and the post-column diversion ratio was 1:4.Some related substances in cefotaxime sodium were identified by comparing the retention time in chromatography,[M+H]⁺ spectrum and MS² spectrum with those of reference substances, the others which haven't reference substances were deduced or speculated by analyzing the MS² or MSⁿ fragmentation with the help of a rule summarized from the MS² fragmentation of cefotaxime sodium and the reference substances of system suitability impurities. RESULTS Twenty-six related substances were separated and detected in the sample, all of which were identified or deduced. They were cefotaxime sodium isomeric compounds and homologs generated during the production process or degradation products. CONCLUSION The method can be applied in the identification and qualitative analysis of the related substances of cefotaxime sodium and the quality control and optimization of the synthesis of cefotaxime sodium.