The current quality standard for polyvinyl alcohol eye drops lacks an impurity assessment,despite the potential impact of raw material impurities on product safety.To strengthen quality control and ensure drug safety,...The current quality standard for polyvinyl alcohol eye drops lacks an impurity assessment,despite the potential impact of raw material impurities on product safety.To strengthen quality control and ensure drug safety,an investigation into the impurity profile of the formulation was conducted,and an HPLC-UV method was developed for impurity quantification.The method validation was performed using an H-type cation exchange column.A total of 116 batches of polyvinyl alcohol eye drops from four manufacturers and two batches of the innovator drug were analyzed.Formic acid was detected exclusively in 0.4 mL samples from Company A and the innovator drug,with concentrations below 0.002%in both cases.Acetic acid was identified in samples from all manufacturers,with levels not exceeding 0.1%.The method demonstrated high specificity and sensitivity,making it well-suited for the quantification of formic and acetic acids in polyvinyl alcohol eye drops.The presence of formic acid was attributed to excipients,whereas acetic acid originated from raw materials and was further generated during pH adjustment in manufacturing.Although the overall impurity levels were low and posed minimal risk to drug safety,manufacturers should remain vigilant regarding impurity control to maintain product quality.展开更多
A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic ...A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.展开更多
A stability-indicating high-performance liquid chromatography（HPLC） method has been developed and validated for the separation and determination of Retigabine and its related substances. The chromatographic separati...A stability-indicating high-performance liquid chromatography（HPLC） method has been developed and validated for the separation and determination of Retigabine and its related substances. The chromatographic separation was achieved on Agilent Eclipse Plus C18 column（4.6 mm×150 mm, 5 μm）. The mobile phase was constituted of triethylamine-phosphate buffer as A and acetonitrile as B. The analysates were then eluted under the gradient conditions as description in this paper. The forced degradation study validated that the newly developed method was specific and selective to the degraded products. The performance of the method was verified according to the present International Conference on Harmonisation（ICH） guidelines for specificity, linearity, accuracy, precision and robustness. The correlation coefficients for Retigabine and its six impurities were greater than 0.999, which was shown in the regression analysis. Limits of detection（LOD） of these impurities were in the range of 0.0092%–0.0103%, indicating the high sensitivity of the newly developed method. Accuracy of the method was determined on the basis of recoveries to be between 96.49% and 118.35% for all impurities. Relative standard derivation（RSD） receiving in the repeatability and intermediate precision experiment, was less than 1.0%. The method can be successfully applied to routine quantify and stability testing Retigabine and its related substances in bulk drugs.展开更多
Aim:Method for the deternination of erythromycin ethylsuccinale(EES)by ion suppression chromatography(ISC)was developed and the influenc factors on ISC were investigated.Methods:A Zorbax SB-C18 column was used with 0....Aim:Method for the deternination of erythromycin ethylsuccinale(EES)by ion suppression chromatography(ISC)was developed and the influenc factors on ISC were investigated.Methods:A Zorbax SB-C18 column was used with 0.02mol.L^(-1)potassium dihydrogen phosphate-acetonitrile(45:55)as mobile phase,The pH and proportion of the mobile phase showed the greatest influences on retention and selectivity.Therefore,the pH of mobile was adjusted to 6.8,the bhest acetonitrile proportion was 55%.The column temperature was maintained at(300±0.5)℃.Acetonitrile was used as solvent for the sample preparation because EES is more stable in it.The flow rate was 1.2mL.min^(-1)and UV detection was performed at 210nm.Results:Under these chromatographic conditions,the main component(erythromycin A ethylsuccinate)and its related substances were separated.The calibration curve showed good linearity over the range of 0.1-1.0mg.mL^(-1),and its correlation coefficient was 0.9998.Conclusion:The method is very suitable for the analysis of erythromycin ethylsuccinate.展开更多
A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp...A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18(150 mm*4.6 mm,5.0 μm) with mobile phase containing 0.2% Triethylamine(TEA) in gradient combination with acetonitrile(ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation;the mass balance was found close to 99.9%.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02%.The method has shown good,consistent recoveries for DTZ(99.8-101.2%) and also for its six known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.展开更多
Objective High performance liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC/MS)methods were developed for the determination of ganciclovir and its related substances.Methods A Hypersil ODS2 co...Objective High performance liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC/MS)methods were developed for the determination of ganciclovir and its related substances.Methods A Hypersil ODS2 column(4.6 mm×250 mm,5 μm)was used with a mobile phase of 0.02 M potassium dihydrogen phosphate buffer(pH 6.0)-methanol(92∶8)at a flow rate of 1.0 mL/min,and UV detector set at 254 nm was used for monitoring the eluents.Results The method was simple,rapid,selective and capable of separating all related substances at trace level with a detection limit of 0.04 μg/mL.It has been validated with respect to accuracy,precision,linearity,and limits of detection and quantification.The linearity range was 10.2-153.0 μg/mL with r=0.9998.The percentage recoveries ranged from 96.7% to 101.6%,and RSD was 1.24%-1.96%(n=5).Conclusion The method was found to be suitable not only for monitoring the reactions during the process development but also for quality control of ganciclovir.For identification of related substances,LC/MS was used.The mainly related substances of ganciclovir active pharmaceutical ingredients(API)were determined as guanine,(1,3-dioxolan-4-yl)methyl acetate,and diacetyl guanine.展开更多
A high-performance liquid chromatography（HPLC） method was developed and validated for the assay of 9-deoxo-9a-aza-9a-homoerythromycin A and related substances that might coexist in products as impurities that origin...A high-performance liquid chromatography（HPLC） method was developed and validated for the assay of 9-deoxo-9a-aza-9a-homoerythromycin A and related substances that might coexist in products as impurities that originate from the synthesis processes. A chromatographic system comprising an ODS 150 mm× 4.6 mm I.D. column, a mobile phase of cetonitrile monobasic potassium phosphate buffer （25/75）, a flow rate of 1.2 mL/min, a temperature of 30 ℃and a UV detector set at 205 nm has shown good chromatographic separation for 9-deoxo-9a-aza-9a-homoerythromycin A and other related substances. The linearity of the calibration curves, the precision, expressed as relative standard deviations, of the HPLC method have been studied. The HPLC method under study was found to be specific, precise, accurate and reproducible, indicating stability.展开更多
Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances suc...Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances such as CA （cholic acid）, DCA （deoxycholic acid）, CDCA （chenodeoxycholic acid） and LCA （lithocholic acid） in raw material and pharmaceutical formulation. Methods： The method was validated for specificity, linearity, accuracy, precision, robustness. A triple quadrupole mass detector was employed, equipped with an ESI （electrospray ionization） source operated in the negative ion mode. The chromatographic system consisted of a Symmetry C 18 column （150 mm × 4.6 mm, id; particle size 5 μm） and methanol-acetonitrile-ammonium acetate （pH 7.6; 10 mM） （40：40：20, v/v/v） as the mobile phase. The chromatographic conditions were 25 uL injection volume, flow rate of 0.4 mL/min and column temperature set at 35℃. Key tindings： The method requires a minimum sample amount and presents very low LOD （limits of detection） for CA （0.29 ng/mL）, DCA （0.59 ng/mL）, CDCA （0.13 ng/mL） and LCA （0.44 ng/mL） in comparison to LC methods coupled to different detectors like UV （ultraviolet）, fluorescence and refractive index. Conclusions： The developed and validated LC-MS/MS method for the determination of UDCA and related substances in raw material and in a suspension was advantageous since it required a minimum sample amount. In turn, it could be used as a stability indicating method.展开更多
HPLC-ESI MS/MS method for relative substances of Mevastatin was established.An Agilent C18 column 250×4.6mm;Mobile phase: acetonitrile-0.05% formic acid (70:30),flow rate 1.0 mL/min,and λ238 nm;MS and MS/MS spec...HPLC-ESI MS/MS method for relative substances of Mevastatin was established.An Agilent C18 column 250×4.6mm;Mobile phase: acetonitrile-0.05% formic acid (70:30),flow rate 1.0 mL/min,and λ238 nm;MS and MS/MS spectra of sample and relative substances were obtained,approximately speculated the structure of relative substances,providing useful information for study and quality control of Mevastatin.展开更多
uring the laboratory optimization and the late phase manufacturing studies of the cholesterol absorption inhibitor Ezetimibe 1, the formation of several stereoisomers was observed. To study the complete stereoisomer p...uring the laboratory optimization and the late phase manufacturing studies of the cholesterol absorption inhibitor Ezetimibe 1, the formation of several stereoisomers was observed. To study the complete stereoisomer profile of Ezetimibe 1, we have synthesized and completely characterized several key stereoisomers of Ezetimibe 1 for the first time. This study will provide an access to the reference standard of these stereoisomers and may have some implications in the development of new medicines.展开更多
基金National Drug Sampling Inspection Project(No.NMPA Drug Admin[2024]1).
文摘The current quality standard for polyvinyl alcohol eye drops lacks an impurity assessment,despite the potential impact of raw material impurities on product safety.To strengthen quality control and ensure drug safety,an investigation into the impurity profile of the formulation was conducted,and an HPLC-UV method was developed for impurity quantification.The method validation was performed using an H-type cation exchange column.A total of 116 batches of polyvinyl alcohol eye drops from four manufacturers and two batches of the innovator drug were analyzed.Formic acid was detected exclusively in 0.4 mL samples from Company A and the innovator drug,with concentrations below 0.002%in both cases.Acetic acid was identified in samples from all manufacturers,with levels not exceeding 0.1%.The method demonstrated high specificity and sensitivity,making it well-suited for the quantification of formic and acetic acids in polyvinyl alcohol eye drops.The presence of formic acid was attributed to excipients,whereas acetic acid originated from raw materials and was further generated during pH adjustment in manufacturing.Although the overall impurity levels were low and posed minimal risk to drug safety,manufacturers should remain vigilant regarding impurity control to maintain product quality.
文摘A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.
基金Natural Science Foundation of Anhui Province(Gr ant No.KJ2014A132)"the Recruitment Program"of Anhui Province Graduate
文摘A stability-indicating high-performance liquid chromatography（HPLC） method has been developed and validated for the separation and determination of Retigabine and its related substances. The chromatographic separation was achieved on Agilent Eclipse Plus C18 column（4.6 mm×150 mm, 5 μm）. The mobile phase was constituted of triethylamine-phosphate buffer as A and acetonitrile as B. The analysates were then eluted under the gradient conditions as description in this paper. The forced degradation study validated that the newly developed method was specific and selective to the degraded products. The performance of the method was verified according to the present International Conference on Harmonisation（ICH） guidelines for specificity, linearity, accuracy, precision and robustness. The correlation coefficients for Retigabine and its six impurities were greater than 0.999, which was shown in the regression analysis. Limits of detection（LOD） of these impurities were in the range of 0.0092%–0.0103%, indicating the high sensitivity of the newly developed method. Accuracy of the method was determined on the basis of recoveries to be between 96.49% and 118.35% for all impurities. Relative standard derivation（RSD） receiving in the repeatability and intermediate precision experiment, was less than 1.0%. The method can be successfully applied to routine quantify and stability testing Retigabine and its related substances in bulk drugs.
文摘Aim:Method for the deternination of erythromycin ethylsuccinale(EES)by ion suppression chromatography(ISC)was developed and the influenc factors on ISC were investigated.Methods:A Zorbax SB-C18 column was used with 0.02mol.L^(-1)potassium dihydrogen phosphate-acetonitrile(45:55)as mobile phase,The pH and proportion of the mobile phase showed the greatest influences on retention and selectivity.Therefore,the pH of mobile was adjusted to 6.8,the bhest acetonitrile proportion was 55%.The column temperature was maintained at(300±0.5)℃.Acetonitrile was used as solvent for the sample preparation because EES is more stable in it.The flow rate was 1.2mL.min^(-1)and UV detection was performed at 210nm.Results:Under these chromatographic conditions,the main component(erythromycin A ethylsuccinate)and its related substances were separated.The calibration curve showed good linearity over the range of 0.1-1.0mg.mL^(-1),and its correlation coefficient was 0.9998.Conclusion:The method is very suitable for the analysis of erythromycin ethylsuccinate.
文摘A stability-indicating liquid chromatographic method has been developed and validated for the determination of Diltiazem Hydrochloride(DTZ) together with its six related substances(Diltiazem sulphoxide,Imp-A,Imp-B,Imp-D,Imp-E,and Imp-F) in a laboratory mixture as well as in a novel tablet formulation developed in-house.Efficient chromatographic separation was achieved on a Hypersil BDS C18(150 mm*4.6 mm,5.0 μm) with mobile phase containing 0.2% Triethylamine(TEA) in gradient combination with acetonitrile(ACN) at a flow rate of 1.0 mL/min and the eluent was monitored at 240 nm.In the developed method,the resolution of DTZ from any pair of impurities was found to be greater than 2.0.The test solution and related substances were found to be stable in the diluent for 24 h.The developed method resolved the drug from its known impurities,stated above,and also from additional impurities generated when the formulation was subjected to forced degradation;the mass balance was found close to 99.9%.Regression analyses indicate correlation coefficient value greater than 0.997 for DTZ and its six known impurities.The LOD for DTZ and the known impurities was at a level below 0.02%.The method has shown good,consistent recoveries for DTZ(99.8-101.2%) and also for its six known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and stability-indicating.
文摘Objective High performance liquid chromatography(HPLC)and liquid chromatography-mass spectrometry(LC/MS)methods were developed for the determination of ganciclovir and its related substances.Methods A Hypersil ODS2 column(4.6 mm×250 mm,5 μm)was used with a mobile phase of 0.02 M potassium dihydrogen phosphate buffer(pH 6.0)-methanol(92∶8)at a flow rate of 1.0 mL/min,and UV detector set at 254 nm was used for monitoring the eluents.Results The method was simple,rapid,selective and capable of separating all related substances at trace level with a detection limit of 0.04 μg/mL.It has been validated with respect to accuracy,precision,linearity,and limits of detection and quantification.The linearity range was 10.2-153.0 μg/mL with r=0.9998.The percentage recoveries ranged from 96.7% to 101.6%,and RSD was 1.24%-1.96%(n=5).Conclusion The method was found to be suitable not only for monitoring the reactions during the process development but also for quality control of ganciclovir.For identification of related substances,LC/MS was used.The mainly related substances of ganciclovir active pharmaceutical ingredients(API)were determined as guanine,(1,3-dioxolan-4-yl)methyl acetate,and diacetyl guanine.
文摘A high-performance liquid chromatography（HPLC） method was developed and validated for the assay of 9-deoxo-9a-aza-9a-homoerythromycin A and related substances that might coexist in products as impurities that originate from the synthesis processes. A chromatographic system comprising an ODS 150 mm× 4.6 mm I.D. column, a mobile phase of cetonitrile monobasic potassium phosphate buffer （25/75）, a flow rate of 1.2 mL/min, a temperature of 30 ℃and a UV detector set at 205 nm has shown good chromatographic separation for 9-deoxo-9a-aza-9a-homoerythromycin A and other related substances. The linearity of the calibration curves, the precision, expressed as relative standard deviations, of the HPLC method have been studied. The HPLC method under study was found to be specific, precise, accurate and reproducible, indicating stability.
文摘Objective： To develop a highly sensitive LC-MS/MS （liquid chromatography-mass spectxometry/mass spectrometry） method applied to the detection and quantitation of UDCA （ursodeoxycholic acid） related substances such as CA （cholic acid）, DCA （deoxycholic acid）, CDCA （chenodeoxycholic acid） and LCA （lithocholic acid） in raw material and pharmaceutical formulation. Methods： The method was validated for specificity, linearity, accuracy, precision, robustness. A triple quadrupole mass detector was employed, equipped with an ESI （electrospray ionization） source operated in the negative ion mode. The chromatographic system consisted of a Symmetry C 18 column （150 mm × 4.6 mm, id; particle size 5 μm） and methanol-acetonitrile-ammonium acetate （pH 7.6; 10 mM） （40：40：20, v/v/v） as the mobile phase. The chromatographic conditions were 25 uL injection volume, flow rate of 0.4 mL/min and column temperature set at 35℃. Key tindings： The method requires a minimum sample amount and presents very low LOD （limits of detection） for CA （0.29 ng/mL）, DCA （0.59 ng/mL）, CDCA （0.13 ng/mL） and LCA （0.44 ng/mL） in comparison to LC methods coupled to different detectors like UV （ultraviolet）, fluorescence and refractive index. Conclusions： The developed and validated LC-MS/MS method for the determination of UDCA and related substances in raw material and in a suspension was advantageous since it required a minimum sample amount. In turn, it could be used as a stability indicating method.
文摘HPLC-ESI MS/MS method for relative substances of Mevastatin was established.An Agilent C18 column 250×4.6mm;Mobile phase: acetonitrile-0.05% formic acid (70:30),flow rate 1.0 mL/min,and λ238 nm;MS and MS/MS spectra of sample and relative substances were obtained,approximately speculated the structure of relative substances,providing useful information for study and quality control of Mevastatin.
基金Sichuan Provincial Science and Technology Support Program (No. 2011SZ0014)
文摘uring the laboratory optimization and the late phase manufacturing studies of the cholesterol absorption inhibitor Ezetimibe 1, the formation of several stereoisomers was observed. To study the complete stereoisomer profile of Ezetimibe 1, we have synthesized and completely characterized several key stereoisomers of Ezetimibe 1 for the first time. This study will provide an access to the reference standard of these stereoisomers and may have some implications in the development of new medicines.
