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??OBJECTIVE To establish an HPLC method to determine the related substances of vortioxetine hydrobromide and identify the degradation products of vortioxetine hydrobromide by HPLC-MS. METHODS An HPLC method was developed by using a CN column(Agilent Zorbax SB-CN,4.6 mm??250 mm, 5 ??m),the mobile phase consisted of CH₃CN-HCOONH₄(50??50, pH adjusted to 5.0 with phosphoric acid),the flow rate was 1.0 mL??min^-1, and the detection wavelength was set at 228 nm. The column temperature was maintained at 25 ??, and the injection volume was 20 ??L. RESULTS Vortioxetine hydrobromide was well separated from the related substances. The detection sensitivity of vortioxetine hydrobromide and its related substances met the determination requirements. The calibration curves of vortioxetine hydrobromide and related substances had good linearity. The repeatability of the method was good(RSD=6.89%, n=6). The average recoveries of the sample were all within 95%-105%. The degradation product produced by oxidation was identified by mass spectrometry as related substance D. CONCLUSION The developed method proves to be simple,accurate,specific and reliable. It can be applied to the determination of vortioxetine hydrobromide and its related substances.     

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??OBJECTIVE To establish an HPLC-HRMS/MS method for analyzing the structures and sources of the related substances in etimicin sulfate. METHODS The chromatographic separation was achieved on a broad pH range column with a basic elution system composed of[H₂O-ammonia-glacial acid(96??3.6??0.4)]-methanol(70??30). Twenty percent of the eluent was detected under positive electrospray ionization(ESI) by Q-Exactive mass spectrometry. The fragmentation pathways were elucidated according to the HRMS and HRMS/MS fragmentation of etimicin and some known compounds. Then the unknown related substances were identified by analyzing their HRMS and HRMS/MS fragmentation with the help of the rule. RESULTS Sixty-five related substances were detected by the HPLC-HRMS/MS method in the two samples from different companies,among which 38 were detected in the product of company A, 59 in that of company B, and 32 were detected for both companies. Fifty-four related substances were identified or deduced, and the other 11 were not able to be identified due to limited information. Based on the significant difference of impurity spectra between the two enterprises, the key parameters of the synthesis process were analyzed. CONCLUSION An HPLC-HRMS/MS method, which showes excellent accuracy, is developed to identify the related substances in etimicin sulfate. The resources and structures of the related substances are analyzed, which will be helpful to the process optimization.     

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??OBJECTIVE To establish a gradient elution method for determination of related substances of azithromycin for injection. METHODS Gradient elution was used for the analysis. A C₁₈ (CAPCELL PAK MG??, 4.6 mm??250 mm,5 ??m)column was used. The mobile phase A consisted of 0.05 mol??L^-1 K₂HPO₄ solution (pH 8.2, adjusted with 20% phosphoric acid)-acetonitrile (45??55), and the mobile phase B was methanol. The flow rate was 1.2 mL??min^-1, and the detection wavelength was set at 210 nm. The column temperature was maintained at 30 ??. The gradient elution program was as follows: 0-35 min, A:75%??95%; 35-64 min, A:75%; 64-65 min, A:95%??75%; 65-71 min, A:75%. RESULTS Azithromycin, near peaks and known impurities were well separated from each other. All acid radicals of azithromycin for injection did not influence the determination of related substances of azithromycin. CONCLUSION This method is more specific than the exising method for determination of related substances of azithromycin, which can more effectively control the quality of the drug.     

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??OBJECTIVE To establish an improved reversed-phase high performance liquid chromatography method coupled with pulsed electrochemical detection for determining the related substances of netilmicin sulfate injection. METHODS Agilent Proshell 120 SB-C₁₈ column (4.6 mm×150 mm,2.7 μm)and gradient elution were used. Mobile phase A was 0.2 mol·L^-1 trifluoroacetic acid in 0.1 mol·L^-1 sodium hydroxide solution-acetonitrile (97:3), mobile phase B was 0.1% pentafluoropropionic acid-acetonitrile (97:3), and the flow rate was 0.8 mL·min^-1. A pulsed electrochemical detector was adopted, and the temperatures of detector and column were kept at 35 ??. The working electrode was a gold electrode with diameter of 3 mm and a quadruple-potential waveform (QPW)was selected as detection waveform. The injection volume was 25 μL. NaOH solution of 0.8 mol·L^-1 was added post-column at a flow rate of 0.3 mL·min^-1. RESULTS A total of 28 impurities could be detected and effective separation was achieved in the typical sample and most of which could not be separated in the method of Ch.P 2015. The linearity of the calibration curve for netilmicin ranged from 0.25 to 15 μg·mL^-1 with a coefficient of determination equal to 0.999 1. The LOD and LOQ of netilmicin were found to be 0.25 ng and 1.25 ng, respectively. The repeatability RSD(n=6) of the single largest impurity and total impurities were 0.9% and 0.8%, respectively. The sample solution was stable within 24 h. CONCLUSION Compared with previously published investigations, the improved method shows higher sensitivity, better separation ability and good reproducibility, especially for differentiating the origin of bulk drug for netilmicin sulfate injection, thus is more suitable for the determination of related substances of netilmicin sulfate injection.     

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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 rapidly identify the related substances in doxycycline hyclate tablets and investigate the possible degradation pathways of doxycycline hyclate solution by 2D-LC-IT-TOF/MS. METHODS Firstly,the chromatography was carried out using the 1stD InertSustain^TM C₁₈(4.6 mm??150 mm,5 ??m) column and a mobile phase containing a mixture of buffer solution(0.25 mol??L^-1 ammonium acetate solution-0.1 mol??L^-1 ethyldiaminetetraacetic acid disodium: triethyiamine=100??10??1)-acetonitrile(85??15). Solution pH was adjusted to 8.8 with glacial acetic acid. Then a InertSustain^TM C₁₈(2.1 mm??50 mm,2 ??m) column was used with 0.1% formic acid-water as mobile A and 0.1% formic acid-acetonitrile as mobile B in a gradient elution mode in 2ndD. Electrospray ionization (ESI) source was tested in both positive and negative ion modes. Nebulized gas flow was 1.5 L?? min^-1. Dry gas flow was 10 L?? min^-1. The desolvation tube temperature was kept at 200 ??. Related substances were characterized according to multi-level MS behaviors. The 2D-LC-IT-TOF/MS method was employed to identify the structures of impurities in forced degradation solutions and illuminate the degradation pathways of doxycycline hyclate solution. RESULTS A total of eight related substances were detected in doxycycline hyclate tablets. Four of them had a content of more than 0.1%, and their structures were identified to be 4-epidoxycycline, metacycline, ??-epidoxycycline and 2-acetyl-2-decarbamoyldoxycycline. The solution of doxycycline hyclate easily degraded under alkaline condition and generated an open loop compound taken off the keto group. The solution was sensitive to heat, and generated 4-epidoxycycline with a little amount of 4-epi-6-epidoxycycline; but the solution was stable under illumination and acidic condition. CONCLUSION The established method is suitable for rapid identification of impurities in doxycycline hyclate, which can be applied as a useful analytical tool for quality control and drug process optimization of doxycycline hyclate.     

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??OBJECTIVE To prevent medication errors during drug subpackage and ensure patients?? medication safety.METHODS Healthcare failure mode and effect analysis (HFMEA) was applied to evaluate the potential failure modes and effects during drug repackaging and dispensing. Thereafter rectification measures was analyzed and carried out in order to prevent the recurrence of failure modes. Risk priority numbers (RPNs) before and after the implication of rectification measures were analyzed using paired t tests.RESULTS After the application of healthcare failure mode and effect analysis, RPN was statistically significantly (P<0.05) reduced by 60% (P=0.000 2), which affecting the incidences of medication errors during drug unit-dose repackaging.CONCLUSION The application of healthcare failure mode and effect analysis can effectively prevent medication errors during drug subpackage and improve patients?? medication safety.     

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??OBJECTIVE To identify the related substances in aituomode bulk drug. METHODS HPLC-QTrap-MS and HPLC-QTOF-MS were used to determine seven kinds of related substances denoted by Imp-A to Imp-G. RESULTS The structures and molecular weights of the related substances in aituomode were identified. CONCLUSION The method is simple and accurate, providing a good idea for the identification of the related substances in bulk drugs. The experimental data are valuable to the determination of the related substances and quality control of aituomode.     

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??OBJECTIVE To establish an HPLC method to determine the related substances of gemcitabine hydrochloride for quality control and observe the stability of gemcitabine hydrochloride. METHODS An HPLC method was used to detect the related substances in gemcitabine hydrochloride. The stability of gemcitabine hydrochloride under various degradation conditions and the stability of its solution at room temperature were studied.RESULTS Impurity Z2 was the main substance detected under each degradation conditions, the amount of Z2 increased proportionally with time at room temperature, and the increased amount exceeded the upper limit of quality standard by 20%(0.02%) at 24 h. CONCLUSION Impurity Z2 markly increases under some degradation conditions and at room temperature, indicating that gemcitabine hydrochloride solution is unstable. The HPLC method has good specificity and linearity, which is suitable for quality control of gemcitabine hydrochloride and its pharmaceutical preparations.     

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??OBJECTIVE To establish the self contrast and correction factor method for the content determination of the related substances in compound ezetimibe and rosuvastatin calcium tablets simultaneously. METHODS RP-HPLC method was adopted. The determination was performed on Kromasil 100-5 C₁₈ Dimensions column (4.6 mm??250 mm, 5 ??m) with mobile phase A consisting of methanol-acetonitrile-0.05 mol??L^-1 potassium dihydrogen phosphate (adjusted to pH 4.0 with phosphoric acid) (10??30??60) and mobile phase B consisting of tetrahydrofuran-acetonitrile-0.05 mol??L^-1 potassium dihydrogen phosphate (adjusted to pH 4.0 with phosphoric acid) (10??50??40) at a flow rate of 1.0 mL??min^-1. The detection wavelength was set at 242 nm. The injection volume was 20 ??l. The slope of linear equation was used to determine the correction factors between ROS impurities 1, 2, 3, EZT impurities 1, 2, 3, 4, 5, 6, 7 and ezetimibe or rosuvastatin calcium. The relative retention time was used to determine the positions of impurities. RESULTS The relative retention time of ROS impurities 1, 2, 3, 4 and EZT impurities 1, 2, 3, 4, 5, 6, 7 to rosuvastatin calcium was 1.5, 1.9, 2.1, 1.1, 1.7, 2.5, 2.6, 2.8, 2.9, 3.0, and 4.0, respectively.The correction factors of ROS impurities 1, 2, 3, 4 and EZT impurities 1, 2, 3, 4, 5, 6, 7 were 1.1, 1.1, 1.0, 1.0, 1.3, 1.1, 1.0, 1.3, 1.4, 0.5, and 1.0,respectively.The content of ROS impurity 4 was 0.15% in three batches of samples, the other impurities were less than 0.1%, and the contents of total impurities were 0.27%, 0.27%, and 0.26%, respectively. CONCLUSION The method is simple,efficient, and accurate for analyzing the related substances in compound ezetimibe and rosuvastatin calcium tablets.     

RP-HPLC测定阿折地平含量及有关物质

阿折地平（azelnidipine）是一种新型的长效钙拮抗剂，可以选择性的阻滞L型钙通道。阿折地平由日本三共制药开发，2003年在日本上市，用于高血压的治疗。关于阿折地平的分析方法笔者尚未见国内报道。本实验建立了用反相高效液相色谱法测定阿折地平含量及有关物质的方法，可用于阿折地平原料药的质量控制。     

RP-HPLC测定舒他兰锌及其有关物质

 目的建立反相高效液相色谱法测定抗癌光敏剂舒他兰锌(Suftalan zinc)含量及有关物质。方法采用SHIMADZU SHIM-PACK VP-ODS色谱柱(4.6 mm×150 mm,5μm),以四氢呋喃-甲醇-N,N二甲基甲酰胺-水-三乙胺(150∶105∶755∶1 000∶1.4,磷酸调pH值6.5～7.0)为流动相,流速1.0 mL·min^-1,紫外可见检测器于677 nm测定。结果RP-HPLC测定的线性范围为20.0～120.1 mg·L^-1,相关系数r=0.999 9;最低检测限为0.048μg;样品溶液至少在3 d内稳定;日内精密度(RSD=0.70%)良好。结论采用反相高效液相色谱法测定抗癌光敏剂(舒他兰锌)含量及有关物质方法简便,结果准确。     

高效液相色谱法测定氨甲环酸注射液的含量和有关物质

 目的 建立反相高效液相色谱法,测定氨甲环酸注射液的含量,并考察其有关物质。方法 以C₁₈柱为固定相;以0.23% 十二烷基硫酸钠溶液（取磷酸二氢钠18.3 g,加水800 mL溶解,加三乙胺8.3 mL混匀后,再加入2.3 g十二烷基硫酸钠,溶解混匀,用磷酸调节pH至2.5,加水至1 000 mL）-甲醇（60∶40）为流动相;检测波长为220 nm。结果 氨甲环酸在0.54～5.38 g·L-1内线性关系良好,相关系数0.999 9,最低检测限75 ng,低、中、高3种浓度的平均回收率分别为99.8%,100.4%,100.1%。结论 本方法准确、简便,专属性强,可用于氨甲环酸注射液的含量测定和有关物质的考察。     

RP-HPLC测定染料木素-4''''-葡萄糖苷及其有关物质

目的 建立染料木素-4'-葡萄糖苷的含量测定方法.方法 采用反相高效液相色谱法.Diamonsil C18柱(4.6 mm×250 mm,5 μm),流动相为乙腈-水(用磷酸调节pH至2.73)(2575),流速1.0 mL·min-1,检测波长261 nm,柱温35℃.结果 染料木素-4'-葡萄糖苷在0.505 5～101.1 mg·L-1内峰面积与浓度呈良好线性关系(r=1.000 0,n=6),平均回收率99.2%(RSD=1.1%,n=9),日内精密度RSD＜0.5%,日间精密度RSD＜0.7%,最低检测限0.2 ng.同时对样品中所含染料木素、染料木素-7-葡萄糖苷和染料木素-7,4'-二葡萄糖苷等微量有关物质的分离和检测也获得满意的结果.结论 该方法简便、可靠,可用于染料木素及其苷类的质量控制.     

RP-HPLC 测定复方盐酸替利定口服液含量及有关物质

 目的 建立一种适用于复方盐酸替利定口服液有关物质及含量测定的高效液相色谱法。 方法 采用 Phenomenex Luna C₈ 柱（ 4.6 mm × 250 mm , 5 μm ）;流动相：甲醇 -0.2% 碳酸氢铵水溶液（ 70 ∶ 30 ）;流速： 1 mL · min^-1 ;检测波长： 229 nm ;柱温： 35 ℃ 。 结果 盐酸替利定和盐酸纳洛酮浓度分别在 0.02 ～ 2 .00 g · L^-1 （ <> r =1.000 0 , <> n= 6 ）和在 0.001 6~ 0.16 g · L^-1 （ <> r= 0.999 8 , <> n= 6 ）内,浓度与峰面积呈良好的线性关系;盐酸替利定和盐酸纳洛酮测定的平均回收率分别为 99.02% 和 98.98% ;盐酸替利定和盐酸纳洛酮的检测限 (S/N<>=3) 分别为 1.0 和 0.4 ng 。 结论 该法简单、快速准确、适用,可同时用于本品中盐酸替利定和盐酸纳洛酮的含量测定及有关物质检查。     

RP-HPLC测定盐酸氨基乙酰丙酸及其散剂的含量及有关物质

 目的用反相离子对高效液相色谱法测定盐酸氨基乙酰丙酸及其散剂的含量及有关物质。方法采用DIKMA IntersilODS-3(4.6 mm×250 mm,5μm)色谱柱,以乙腈-离子对缓冲液(取磷酸二氢铵1.15 g,辛烷磺酸钠2.16 g,加水800 mL使溶解,用磷酸调节pH值至2.0,加水稀释至1 000 mL)(18∶82)为流动相,检测波长为205 nm。结果盐酸氨基乙酰丙酸的有关物质与主成分的分离度及检出灵敏度完全达到要求,两个主要杂质邻苯二甲酸最小检测量为0.1 ng,5-邻苯二甲酰亚胺乙酰丙酸最小检测量为0.25 ng。盐酸氨基乙酰丙酸在0.200 7～1.806 3 g·L^-1内,其峰面积与浓度呈良好的线性关系,相关系数(r=0.999 9)。平均回收率为99.8%(RSD=0.9%,n=9)。结论该方法准确、简便、快速,可用于盐酸氨基乙酰丙酸及其散剂的质量控制。     

RP-HPLC测定染料木素-4′-葡萄糖苷及其有关物质

 目的建立染料木素-4′-葡萄糖苷的含量测定方法。方法采用反相高效液相色谱法。Diamonsil C₁₈柱(4.6mm×250mm,5μm),流动相为乙腈-水(用磷酸调节pH至2.73)(25∶75),流速1.0mL·min^-1,检测波长261nm,柱温35℃。结果染料木素-4′-葡萄糖苷在0.5055～101.1mg·L^-1内峰面积与浓度呈良好线性关系(r=1.0000,n=6),平均回收率99.2%(RSD=1.1%,n=9),日内精密度RSD<0.5%,日间精密度RSD<0.7%,最低检测限0.2ng。同时对样品中所含染料木素、染料木素-7-葡萄糖苷和染料木素-7,4′-二葡萄糖苷等微量有关物质的分离和检测也获得满意的结果。结论该方法简便、可靠,可用于染料木素及其苷类的质量控制。     

高效液相色谱法测定苯磺酸氨氯地平的含量及有关物质

 目的建立反相高效液相色谱法,测定苯磺酸氨氯地平的含量,并考察原料药中的有关物质。方法采用HPLC-UV法,并考察色谱条件、优化分离效果;以C₁₈柱(4.6 mm×250 mm,5μm)为固定相;流动相为乙腈-甲醇-10 mmol·L^-1磷酸二氢钾(含0.8%三乙胺,磷酸调pH3.0)(35∶10∶55),流速1.0 mL·min^-1;柱温30℃,检测波长为236 nm。采用内标法定量,吲达帕胺为内标物。结果苯磺酸氨氯地平在0.0103～0.5145g·L^-1内线性关系良好,相关系数为0.9999,最低检测限10ng。高、中、低3种质量浓度的平均回收率分别为(98.48±0.26)%、(99.34±0.44)%和(101.23±0.07)%;苯磺酸氨氯地平原料药的平均含量为(100.41±0.51)%。结论本方法准确、灵敏,精密度高、专属性强,可用于苯磺酸氨氯地平含量测定及有关物质的考察。     

RP-HPLC测定依折麦布原料药中的有关物质

目的: 建立测定依折麦布原料药中有关物质的RP-HPLC测定法。方法: Phenomenex Luna C₁₈色谱柱(4.6 mm ×150 mm,5 μm),流动相0.01%磷酸(A),乙腈(B),梯度洗脱,流速1.0 mL·min^-1,检测波长231 nm,柱温35℃。结果: 依折麦布与有关物质分离良好;有关物质A,B,C在0.035~0.8 mg·L^-1峰面积与浓度呈良好的线性关系,r分别为0.999 7,0.999 4,0.999 9(n=6)。结论: 方法操作简便,灵敏度高,专属性强,重复性好,可用于依折麦布原料药中有关物质的检查。     

RP-HPLC测定羟苯磺酸钙含量及有关物质

目的:建立反相高效液相色谱法测定羟苯磺酸钙原料药的含量及其有关物质.方法:采用C8色谱柱(4.6 mm×200 mm,5μm),柱温35℃,50 mmol·L-1磷酸二氢钠溶液-乙腈(90∶ 10)为流动相等度洗脱,流速0.8 mL·min-1,检测波长220 nm,进样体积20 μL.结果:含量测定色谱条件下,羟苯磺酸钙质量浓度在20.0 ～ 200.0 mg·L-1与峰面积呈良好的线性关系(r=0.999 5),平均回收率99.4％;有关物质项下杂质氢醌的含量分别为0.018％,0.023％,0.021％,杂质总量分别为0.16％,0.18％,0.13％.结论:方法简便、快速,可用于羟苯磺酸钙原料药的含量测定及有关物质的检查.