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??OBJECTIVE To establish an analytical method for simultaneous determination of scutellarin ethyl ester and its related substances by RP-HPLC and identify the main related substances by UPLC-MS.METHODS The assay was performed on a Kromasil C₁₈ column(4.6 mm??250 mm,5 ??m),and gradient elution was used with methanol-water containting 0.2% formic acid. The flow rate was 1.0 mLmin^-1and the detection wave length was set at 335 nm.The structure of the main related substance was identified by high resolution MS.RESULTS Under the separation condition,the related substances were completely separated from the principal components.The calibration curve of scutellarin ethyl ester showed good linearity in the concentration range of 5.005-1 001 mgL^-1(r²=0.999 9). The average recovery was 99.6%. The main related substance was identified as scutellarin by LC-MS. The contents of total impurities and scutellarin were 1.14% and 0.89%, respectively.CONCLUSION The method is simple, efficient and accurate, and can be used for the quality control of scutellarin ethyl ester.     

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??OBJECTIVE To develop an LC-MS/MS method for the determination of vonoprazan pyroglutamate and vonoprazan fumarate in rat urine to determince the urine excretion of the two drugs in SD rats. METHODS The detection was performed on an API 4000 tandem mass spectrometer equipped with an electrospray ionization (ESI) source. Multiple reaction monitoring (MRM) was selected with the transitions of m/z 346.2 to 315.2 for TAK-438 P and m/z 237.2 to 194 for IS, respectively. Separation of the analytes was achieved by a Shimadzu liquid chromatography system with an Agelient C₁₈ analytical column (4.6 mm??150 mm, 3.5 ??m). Isocratic elution was adopted with mobile phase A (10 mmol??L^-1 ammonium acetate and 0.1% formic acid) and mobile phase B (methanol) at the ratio of 40??60, at a flow rate of 0.6 mL??min^-1. The total run time was 6 min and the injected sample volume was 5 ??L. All the features of the developed method suggested it met the criteria for bioanalytical METHODS recommended by regulatory authorities. The accumulative urine excretion rates of TAK-438 F and TAK-438 P were determined after oral administration of TAK-438 P and equimolar TAK-438 F in SD rats.RESULTS The accumulative urine excretion rates of the prototype drugs were 2.11% and 2.03%, respectively. The low excretion rates indicated that metabolism might be the major clearance mechanism of TAK-438 P and TAK-438 F. CONCLUSION This was the first time to establish and validate a simple, rapid and sensitive LC-MS/MS method for the quantification of TAK-438 P. There is no significant difference of the accumulative urine excretion rate between TAK-438 P and TAK-438 F in SD rats, which provides the basis for the druggability of TAK-438 P.     

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??OBJECTIVE To study the content determination method of crotamiton. METHODS The quantitative mass balance method, HPLC external standard method and nuclear magnetic resonance(QNMR) were used to determine the content of crotamiton, respectively. The accuracy of the three methods was evaluated. RESULTS The contents of crotamiton were 99.2%,102.9% and 99.1% respectively as determined by the three different methods. CONCLUSION Because the ultraviolet absorption coefficients of cis- and trans-crotamiton might be different, the current pharmacopoeia method, ie, using integrated peak areas to calculate the content, is questionable. QNMR method can measure the contents of cis- and trans-crotamiton respectively, so it can be a complementary method to establish the reference standard.     

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??OBJECTIVE To compare the HPLC-PAD method and HPLC-ELSD method for determination of related substances in spectinomycin hydrochloride for injection, and determine 31 batches of samples by the two methods. METHODS The following conditions were used for both methods:the analytical column was Apollo C₁₈ column (4.6 mm??250 mm,5 ??m), mobile phase was 0.1 mol??L^-1 trifluoroacetic acid solution, the column temperature was maintained at 30 ??, and the sample volume was 20 ??L. For the PAD detection, gold electrode (3 mm)was used as the detection electrode, Ag-AgCl as reference electrode, titanium alloy as counter electrode, and integrated amperometric detector was employed with four waveform detection potential. For the ELSD detection, the drift tube temperature was set at 110 ??, and the carrier gas flow rate was 2.6 L??min^-1, with gain of 1. RESULTS The two methods were consistent in the species and number of detected impurities. The detection limits of the PAD method and ELSD method were 2.4 and 72.8 ng, respectively (S/N=3). For the PAD method there existed a direct linear relationship in the concentration range of 0.15-150 ??g??mL^-1, while a double logarithmic linear relationship was shown in the concentration range of 17-170 ??g??mL^-1 for the ELSD method. When 31 batches of samples were determined for related substances by the two kinds of methods, the contents of impurity D and E were basically the same, but there were significant differences in the contents of impurity A and (4R)-dihydrospectinomycin. After correction, the contents of impurity A and total impurities determined by the PAD method were consistent with those by the ELSD method. CONCLUSION The two methods can both effectively detect the related substances of spectinomycin to achieve the purpose of controlling related substances. When using HPLC-PAD method, the impurity A and (4R)-dihydrospectinomycin should be adjusted by using response factor or the reference substances. The ELSD method needs to use double log linear regression.     

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??OBJECTIVE To explore the accumulation rules of the effective constituents in Ophiopogonis Radix to provide theoretical support for its production and quality control. METHODS Ophiopogonis Radix samples in different growth phases were harvested, and the total polysaccharides, total flavones, and total saponins in the sampleswere measured by ultraviolet spectrophotometry. Methylophiopogonanone A, ophiopogonin C, ophiopogonin D, and ophiopogonin D?? were determined by HPLC. RESULTS The contents of total polysaccharides, total flavones, and total saponins in Ophiopogonis Radix were positively correlated with root growth time. The contents of three categories of constituents increased with the prolongation of root growth time, but the accumulative rate was inconsistent in different growth phases, which had a slight decrease after reaching the maximum at the end of March. The accumulation trend of six single components were basically the same to the three categories of constituents. For samples with same harvest time, the content of the main constituents was higher in the samples treated by paclobutrazol than those without paclobutrazol treatment. CONCLUSION The variation trend of the main chemical components in Ophiopogonis Radix is basically the same to that of the root growth. Methylophiopogonanone A and phiopogonin D are the most representative, and they could be taken as evaluation index to guide production and quality control of Ophiopogonis Radix.     

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??OBJECTIVE To establish a new dissolution method of Ligustrazine Phosphate Pills, which provides reference for revising the quality standard. METHODS The dissolution media were hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.5), phosphate buffer solution(pH 6.8) and water. The dissolution curves of six batches of Ligustrazine Phosphate Pills in the four kinds of dissolution media were compared to establish the dissolution method. Apparatus 2 was used for the new method of dissolution test,using 500 mL water as the dissolution medium,at the rate of 75 r??min^-1. The dissolution solution was taken at 20 min and analyzed by HPLC. The dissolution limit was set at 80%. RESULTS The dissolution curves of the six batches of samples were similar in the four kinds of dissolution media. The pills were dissolved completely within 15 min. CONCLUSION The determination method is highly reproducible, accurate and reliable, which can objectively reflect the dissolution of ligustrazine phosphate pills, and provides a basis for the reasonable unification and revision of the dissolution test of the current quality standard.     

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??Chrysanthemum morifolium has a long history of culture and use in China. Due to different germplasm resources, producing areas, and processing methods, many cultivated varieties have formed now. The varieties and processing methods of C. morifolium are affected by economic interests and processing cost, which change gradually. On the basis of spot investigation and related literature study, the changes of the varieties and processing methods of C. morifolium were summarized in this paper. It will provide theoretical evidence for the culture, processing, quality evaluation, and clinical application of C. morifolium.     

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??OBJECTIVE To evaluate the bioequivalence of cefdinir suspension and reference cefdinir capsule in Chinese healthy male subjects.METHODS A single oral dose of 100 mg cefdinir suspension or cefdinir capsule was given to 24 subjects according to a 2-way crossover design. The plasma concentrations of cefdinir were determined by UPLC-MS/MS. The pharmacokinetic parameters were calculated and bioequivalence was compared by WinNonlin 6.3 program. RESULTS The main pharmacokinetic parameters of cefdinir suspension and cefdinir capsule were as follow: ??_max were (1 034.78??358.17), (969.71??297.38) ng??mL^-1;t_max were (2.98??0.60), (3.44??0.70) h; AUC_0-12 were (4 911.24??1 675.30), (4 522.35??1 600.13) ng??h??mL^-1; AUC_0-?? were (5 026.24??1 735.32),(4 680.69??1 699.93) ng??h??mL^-1;t_1/2 were (1.71??0.23), (1.79??0.39) h. The 90% confidential interval of ??_max, AUC_0-12, AUC_0-?? of tested formulation were 95.6%-115.3%, 99.9%-117.2%, 99.0%-116.0%. CONCLUSION The two formulations are bioequivalent.     

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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 the HPLC fingerprint of Rhodiola crenulata herbs from Sichuan plateau, and compare them with commercially available samples. METHODS RP-HPLC analysis was applied using Agilent Zorbax C₁₈ chromatographic column (4.6 mm??250 mm,5 ??m). The mobile phase A was 0.1% formic acid aqueous solution and mobile phase B was 0.1% formic acid in acetonitrile. The flow rate was 1 mL??min^-1 and the column temperature was maintained at 35 ??. The detection wavelength was set at 245 nm and injection of sample was 20 ??L. The traditional Chinese medicine fingerprint chromatogram similarity evaluation system (Version 2004A), principal component analysis, and cluster analysis were used to compare 30 Rhodiola crenulata samples from various locations based on their HPLC chromatograms. RESULTS The established HPLC fingerprint of Rhodiola crenulata was able to analyze Rhodiola crenulata from different sources. CONCLUSION The method has good repeatability and stability, and can be used for the quality management standard of Rhodiola crenulata.     

口腔崩解片体外崩解评价方法探讨

 目的改进设计口腔崩解片体外崩解的评价方法。方法制备了利培酮口腔崩解片和茶苯海明口腔崩解片,改进设计了4种口腔崩解片体外崩解的测定方法。分别采用这些方法测定了两种口崩片的体外崩解,并且考查了体内外相关性。结果对于利培酮口崩片,采用滴定管液滴法测定崩解具有较好的重现性和较好的体内外崩解时间相关性,而且砂砾感(粒度)控制准确;对于茶苯海明口崩片,则以日本药典(JP)溶出度改良法较为适合。结论用于口崩片体外崩解评价,滴定管液滴法和JP溶出度改良法为两种可取的方法。     

口腔崩解片的研究进展

口腔崩解片是非常有特点且很有开发利用前景的口腔用固体制剂,为更好的促进口腔崩解片的发展,给临床用药提供参考,通过查阅文献,从口腔崩解片的特点、辅料选择、制备方法、技术要求及质量控制方面进行综述。     

豆腐果苷口腔崩解片的制备

 目的以微晶纤维素(MCC),交联聚乙烯吡咯烷酮(PVPP)和泡腾剂(碳酸氢钠与枸橼酸比例为1∶1.2)为崩解剂制备豆腐果苷口腔崩解片。方法采用粉末直接压片法制备,运用星点设计-效应面法进行处方优化,并对药物体外溶出进行评估。结果以MCC,PVPP和泡腾剂含量为自变量,体外崩解时间为因变量进行二次多项式拟合,结果表明,拟合的效果较好,较优处方为MCC 5.4%、PVPP 5.8%、泡腾剂12%。与市售普通片比较,口腔崩解片具有明显速释效果。结论将豆腐果苷制成口腔崩解片能显著提高其体外溶出速度。     

布南色林口腔崩解片制备工艺的研究

目的：采用正交试验筛选布南色林口崩片的处方,并测定其溶出度。方法：以内崩解剂微晶纤维素的用量、填充剂乳糖的用量、外崩解剂交联羧甲基淀粉钠的用量为考查因素,以口崩片的崩解时间（td）、润湿时间（t）和混悬稳定性（△A）为评价指标进行正交试验,确定最佳处方;对优化处方所制样品测定其溶出度。结果：优选工艺为微晶纤维素30％、乳糖15％、交联羧甲基淀粉钠10％,所制样品平均td为19．8s,t为20．1s,△A为0．0016;30s内药物基本溶出完全。结论：所选处方制备的样品符合《中国药典》相关规定。     

灯盏花素口腔崩解片质量标准的研究

目的:对灯盏花素口腔崩解片进行质量标准研究。方法:用薄层色谱法鉴别灯盏花素口腔崩解片中主要成分野黄芩苷,高效液相法测定该制剂中野黄芩苷的含量进行质量检查;并测定其崩解时限、溶出度和片重差异。结果:灯盏花素口腔崩解片能在30 s内崩解完全,且片重差异符合规定;其溶出速度与市售灯盏花素片比较显著加快。野黄芩苷在0.081 6μg~0.408 0μg范围内,色谱峰面积与进样量间线性关系良好,r=0.999 9,平均回收率为99.67%,RSD为0.47%。结论:建立了该制剂的质量标准,其鉴别与含量测定方法简便、可靠,可作为该制剂的质量控制指标。     

增损八珍口崩片处方的优化

目的增损八珍口崩片处方筛选和制备工艺的优化。方法以口崩片的崩解时限和口感为指标,采用正交试验设计对增损八珍口崩片的处方进行优化。结果口崩片的最佳处方为微晶纤维素用量为36%、交联聚乙烯吡咯烷酮用量为8%、交联羧甲基纤维素钠用量为8%、泡腾剂用量为12%。结论按优选处方制得的增损八珍口崩片崩解迅速,硬度适宜,口感良好,符合设计要求。     

银黄口腔崩解片的质量控制方法研究

目的:建立银黄口腔崩解片的质量控制方法。方法:采用薄层鉴别方法鉴别银黄口腔崩解片的黄芩和金银花药材,采用反相高效液相色谱法测定君药黄芩主要有效成分黄芩苷的含量。结果:薄层色谱同时检出黄芩苷和绿原酸斑点,阴性无干扰。银黄口腔崩解片崩解时限小于1 min。黄芩苷HPLC测定的条件为:十八烷基硅烷键合硅胶为填充剂,甲醇-水-磷酸(47∶53∶0.2)(v/v)为流动相;检测波长为280 nm;黄芩苷线性回归方程为Y=8 177 827X-34 818,r=0.999 5(黄芩苷进样量范围1.24~0.04μg),平均回收率为100.03%(RSD为2.32%);本品每片含黄芩苷(C_(21)H_(18)O_(11))不得少于18.0mg。结论:建立的质量控制方法简单方便、科学可行。     

陈皮口腔崩解片中橙皮苷的含量测定

目的：建立陈皮口腔崩解片中橙皮苷的含量测定方法。方法：采用C18柱；流动相：甲醇－醋酸－水（35：4：61）；检测波长：283nm；结果：橙皮苷的线性范围为0．356～2．848μg，r=0．9998；平均回收率为97．5％，RSD=1．23％。结论：本含量测定方法准确、稳定，可用于陈皮口腔崩解片的质量控制。     

丹参多酚酸钠口腔崩解片制备工艺研究

目的:筛选丹参多酚酸钠口腔崩解片的制剂处方和制备工艺。方法:以崩解时间、口感和外观为主要测定指标,采用直接压片法制备丹参多酚酸钠口腔崩解片,在筛选辅料的基础上进行正交优化处方设计,确定处方的组成。结果:崩解时间在30s左右,外观及口感均良好。结论:丹参多酚酸钠口腔崩解片处方符合要求,崩解时间能控制在30s左右,口感及外观良好,制备工艺简易,适合大批量生产。     

关于中成药口腔崩解片开发应用的思考

通过对口腔崩解片的特点及主要制备工艺的分析 ,结合当前中成药工业的现状及具体实际 ,认为口腔崩解片可以应用于中成药制剂的开发。