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OBJECTIVE To establish the method for content determination of related substances in Oxcarbazepine tablets. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted and the separation was performed on ZORBAX Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate solution （pH6.0） （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was 230 nm and column temperature was set at 35 ℃. The sample size was 10 μL. RESULTS The linear ranges of oxcarbazepine and impurity A， B， C， D， E， I， K， L and N were 0.192-1.440， 1.019-7.639， 0.208-1.559， 0.230-1.727， 0.389-2.915， 0.182-1.364， 0.393-2.945， 0.199-1.493， 0.199-1.490 and 0.200- 1.503 μg/mL， respectively （all r＞0.999）. The detection limits were 0.046， 0.037， 0.049， 0.027， 0.077， 0.040， 0.114， 0.054， 0.055 and 0.039 μg/mL. The quantitation limits were 0.152， 0.122， 0.162， 0.090， 0.258， 0.132， 0.380， 0.181， 0.185 and 0.130 μg/mL. RSDs of precision， repeatability， stability （24 h） and durability tests were all lower than 5.0%. The average recoveries were 92.8%-105.6% （RSD≤3.0%， n＝9）. Only impurity K and unknown impurity were detected in the original preparation sample， with a total content of 0.078% to 0.083%； impurities A， B， D， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅰ， with a total content of 0.147% to 0.163%； impurities A， B， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅱ， with a total content of 0.085% to 0.161%. CONCLUSIONS The established method is rapid， sensitive， accurate， stable and durable. It can be used for the content determination of 9 known impurities in Oxcarbazepine tablets.
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For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL-1 (r = 1.000 0), 0.244-9.75 µg·mL-1 (r = 0.999 9), 0.244-4.80 µg·mL-1 (r = 0.999 9), 0.254-1.02 µg·mL-1 (r = 0.999 9), and 0.247-0.987 µg·mL-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.
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@#TA method for the content determination of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II) was established in order to investigate their level in 155 batches of this product, and to explore the reason for the generation of these two impurities.The determination was performed on an Agilent Poroshell 120 EC-C18 column with mobile phases of sodium acetate/tetrahydrofuran solution (A) and sodium acetate solution -acetonitrile-methanol (B, 200∶400∶400) (gradient elution) at the flow rate of 0.5 mL/min.The excitation wavelength and the emission wavelength of the fluorescence detector were 233 nm and 441 nm, respectively.The column temperature was 40 °C, and the injection volume was 8 μL.The contents of methionine sulfoxide and methionine sulfone from 155 batches of compound amino acid injection (18AA-II) was determined using this method, and the residual oxygen content was detected by headspace gas analyzer.The results showed that the linear range of methionine sulfoxide and methionine sulfone were 0.128 1-10.250 0 μg/mL (r = 0.999 9) and 0.261 0-10.440 0 μg/mL (r = 0.999 8), respectively.The limits of quantitation were 0.13 μg/mL and 0.26 μg/mL, respectively; the limits of detection were 0.04 μg/mL and 0.09 μg/mL, respectively.RSDs of precision, stability and repetitive test were all lower than 1.3%.The recoveries ranged 98.00%-100.79% (RSD = 1.15%, n = 9) and 98.19%-102.31% (RSD = 1.33%, n = 9).The content level of oxidized related substances from different manufacturers showed significant difference, showing relevance with the residual oxygen content to some extent, yet no significant correlation with the added amount of antioxygen (sodium pyrosulfite).The method is validated to be useful for the content control of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II).It is quite necessary to include the determination of oxidized related substance into the quality specification.Manufacturers should strengthen the control of remaining oxygen in their products.
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OBJECTIVE：To establish the m ethod for the simultaneous determination of 6 carbohydrate related substances in glucose as fructose ，maltose，isomaltose，maltotriose，maltotetraose and maltopentaose. METHODS ：HPLC-ELSD was adopted. The determine was performed on XBridge Amide column with mobile phase consisted of acetonitrile-water （75∶25，V/V）at a flow rate of 0.5 mL/min. The column temperature was set at 30 ℃，and the sample size was 10 L. The detector was evaporative light scattering detector ，the carrier gas was nitrogen ，the gas pressure was 40 psi，the evaporation temperature was 80 ℃，the drift tube temperature was 80 ℃，and the gain was 100. RESULTS ：The linear range of 6 carbohydrate related substances were 5.99-59.88， 9.90-98.96，9.92-99.19，5.97-59.74，4.03-40.32，5.89-58.89 μg/mL（r＞0.999 0）. The quantitation limits were 1.5，1.5，1.5，3.0， 3.0 and 3.0 μg/mL，respectively. The detection limits were 0.5，0.5，0.5，1.0，1.0，1.0 μg/mL，respectively. RSDs of precision ， stability（12 h）and reproducibility tests were all lower than 2.0％. The average recoveries were 95.87％-98.59％（RSD＝1.04％，n＝ 9），95.66％-99.84％（RSD＝1.20％，n＝9），96.11％-98.97％（RSD＝1.04％，n＝9），95.06％-99.11％（RSD＝1.25％，n＝9）， 95.69％-98.22％（RSD＝0.83％，n＝9），95.34％-98.56％（RSD＝1.01％，n＝9）. The contents of 6 carbohydrate related substances in 9 batches of glucose were 1.26-2.22，2.55-3.36，2.37-3.37，1.28-2.01，0-2.11 and 0-1.89 mg/g，respectively. CONCLUSIONS ： Established method is accurate and sensitive ，and can be used for the detection of carbohydrate related substances in glucose.
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Based on fingerprint and network pharmacology,the whole process quality control of Zhuru Decoction was conducted and efficacy-related substances were predicted.The fingerprints of raw materials,decoction pieces and Zhuru Decoction were established,and 25 common peaks were identified,including 9 common chromatographic peaks of 3'-hydroxy puerarin,puerarin,3'-methoxy puerarin,puerarin,aperioside,daidzin,daidzein,liquiritin,glycyrrhizic acid and 6-gingerol, with similarity all greater than 0.95.The main groups of pharmacodynamic substances can be transferred from raw materials,decoction pieces to Zhuru Decoction step by step,with a clear affiliation relationship.Based on the testability and traceability,the active ingredients were screened,and the network relationship of "component-target-pathway" was constructed and analyzed for the nine chemical components screened by network pharmacology.The enriched pathways included energy metabolism,alcoholism,and smooth muscle contraction and relaxation-related pathways.The nine active components of Zhuru Decoction may achieve the effects of clearing heat, alleviating a hangover, harmonizing stomach and stopping vomiting through these signaling pathways.Based on transitive and traceable properties of the above 9 components as well as their close relationship to the efficacy of Zhuru Decoction,these 9 components can be identified as potential efficacy-related substances and provide basis for the overall quality control of Zhuru Decoction.
Subject(s)
Drugs, Chinese Herbal , Glycyrrhizic Acid , Prescriptions , Quality ControlABSTRACT
OBJECTIVE: To establish a method for analysis of related substances in biapenem with micellar electrokinetic capillary chromatography(MEKC). METHODS: In order to improve the separation selectivity, a zwitterionic surfactant, 3-(N, N-dimethylhexadecylammonium)-propanesulfonate(PAPS) was used. The optimal separation conditions were as follows: the total length of the capillary was 48.5 cm (the effective length was 48 cm), the buffer was 90 mmol•L-1 tris(hydroxymethyl)aminomethane (tris)-phosphate buffer containing 17 mmol•L-1 PAPS and 3 mg•mL-1 polyoxyethylene 23 lauryl ether (Brij 35), the applied voltage was 22 kV, and the capillary temperature was controlled at 30℃. Further more, the specificity, linearity, precision, repeatability, stability and durability were studied. The contents of related substances in biapenem commercial samples were analyzed. RESULTS: The MEKC method, which was a comparable analysis method to HPLC, successfully separated the adjacent impurities of biapenem by using the zwitterionic surfactant PAPS. The specific test showed that this method was especially suitable for the detection of biapenem dimers A, B and open-ring compound. CONCLUSION: In this method, MEKC with zwitterionic surfactant is for the first time applied to the analysis of related substances in biapenem (amphoteric drugs). It provides a feasible analysis method with high sensitivity, good specificity and reproducibility for the quality control of biapenem.
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Objective: To establish a high performance liquid chromatography(HPLC)method for determination of the related substances of carbaindoline hydrochloride tablets. Methods: HPLC was performed on an octadecylsilane bonded silica gel column. The mobile phase was acetonitrile/0.01 mol/L KH2PO4 solution in a gradient elution. The flow rate was 1.0 ml/min. Column temperature was 25℃. Injection volume was 10 μl. The detection wavelength was 210 nm. Methodological verification was carried out and the changes of related substances under different influencing conditions were investigated using the verified method. Results: The carbaindoline hydrochloride and related substances were all well separated under the conditions of the established method. The limit of detection(LOD)and quantitation(LOQ)of the method were 0.5 ng and 1.5 ng, respectively. The calibration curve was linear in the range of 2.0-7.0 μg/ml(r=0.9995). The RSD of reproducibility was 0.05%. The carbaindoline hydrochloride tablets showed colored changes with a significant increase of related substances under light illumination or at higher temperature of 60℃. Conclusion: The established method is simple, acurate, sensitive and specific, which might be used for the determination of related substances in carbaindoline hydrochloride tablets. The carbaindoline hydrochloride tablets produced more impurities under the light illumination or at the higher temperature, which indicates that they should be stored at room temperature avoiding light.
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@#By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.
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OBJECTIVE：To establish the method for content determination of related substances in Paracetamol tablets. METHODS：HPLC method was adopted. The determination was performed on Agilent 5HC-C8 column with mobile phase A consisted of methanol-water-glacial acetic acid （50 ∶ 950 ∶ 1，V/V/V）and mobile phase B consisted of methanol-water-glacial acetic acid（500 ∶ 500 ∶ 1，V/V/V）（gradient elution ）at the flow rate of 0.9 mL/min. The detection wavelength was set at 254 nm，and column temperature was 40 ℃. The sample size was 5 μL. RESULTS：Under the chromatographic condition ，the resolutions of main component （paracetamol），6 known impurities （p-aminophenol，p-chloroacetanilide，impurity A ，B，D，F），3 specific excipients（methyl hydroxybenzoate ，ethyl hydroxybenzoate ，propyl hydroxybenzoate ）and 1 unknown impurity were all higher than 1.5. The linear range of 6 known impurities were 0.539-1.617，0.026-0.384，0.237-17.799，0.257-19.271，0.239-17.955， 0.246-18.462 μg/mL（r≥0.999 8），respectively. Correction factors of impurity A ，B，D，F were 2.9，1.0，1.2，6.2. The limits of detection were 0.009 6，0.024 2，0.164 0，0.051 1，0.055 9，0.422 0 ng；the limits of quantitation were 0.032 0，0.080 6，0.546 0，0.170 0，0.186 0，1.406 0 ng. Average recoveries were 95.96％-111.09％（RSDs were 0.05％-2.42％）. The RSDs precision test were low than 15％，and the durability were good. p-aminophenol（all were 0.006％），impurity B （0.016％-0.017％）and unknown impurity（0.002 0％-0.002 1％）were detected in 3 batches of sample. p-choroacetanilide，impurity A ，D and F were not detected. CONCLUSIONS：The method is specific ，accurate and suitable for the determination of related substance in Paracetamol tablets.
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OBJECTIVE：To establish UPLC method for the content determination of related substances in Terlipressin for injection. METHODS ：UPLC method was used to determine the contents of related substances in 5 batches of Terlipressin for injection. The separation was performed on Xtimate UPLC C 18 column with mobile phase A consisted of ammonium sulfate buffer （pH 2.3）-methanol（90 ∶ 10，V/V）and mobile phase B consisted of ammonium sulfate buffer （pH 2.3）-methanol（60 ∶ 40，V/V） （gradient elution ）at the flow rate of 0.2 mL/min. The detection wavelength was set at 210 nm，and sample size was 5 μL. RESULTS：The linear range of impurity A ，B，C，D，F，H，I，K，L and N were 0.43-3.86，0.44-3.95，0.44-3.97，0.45-4.08， 0.45-4.05，0.50-4.50，0.47-4.26，0.47-4.23，0.46-4.13，0.44-3.96 μg/mL（r≥0.999 7），respectively. The detection limits were 0.04， 0.04，0.05，0.04，0.05，0.05，0.05，0.05，0.04 μg/mL. The quantitation limits were 0.13，0.13，0.14，0.13，0.15，0.14，0.14， 0.14，0.13 μg/mL，respectively. RSDs of precision ，reproducibility and stability tests were all lower than 8％. The average recoveries were 94.95％，97.81％，101.88％，95.26％，93.40％，102.48％，104.26％，102.31％，96.42％，90.42％，with RSD s of 1.89％，1.86％，0.68％，1.30％，1.98％，3.36％，1.26％，1.30％，1.19％，1.40％（n＝9），respectively. Total contents of impurities in 5 batches of Terlipressin for injection were all lower than 4％. CONCLUSIONS ：Established method is rapid ，simple， accurate and specific ，which can be used for the quantitative analysis for related substances in Terlipressin for injection.
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OBJECTIVE：To establish a method for the determination of related substances in dibasol hydrochloride raw materials and tablets ， and to predict the maximum unknown impurity ’s structure. METHODS ： The related substances （o-phenylenediamine，phenylacetic acid ）in dibasol hydrochloride raw materials and tablets were determined by HPLC. The determination was performed on Kromasil C 18 column with mobile phase consisted of mobile phase-methanol-glacial acetic acid-triethylamine（45 ∶ 55 ∶ 0.5 ∶ 0.5，V/V/V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 220 nm，and column temperature was 30 ℃. Sample size was 10 μL. UPLC-TOF-MS，1H-NMR and 13C-NMR were used for structure prediction. The determination was performed on Waters Acquity UPLC BEH C 18 column with mobile phase consisted of water-methanol （45∶55， V/V）at the flow rate of 0.2 mL/min. The column temperature was 30 ℃，and sample size was 1 μL. The ion source was electrospray ion source . The scanning mode was negative ion scanning mode. The first-order mass spectrum scanning range was m/z 100-800，the capillary voltage was 3 000 V，the source temperature was 100 ℃，the desolvent gas was nitrogen ，and the solvent free gas flow rate was 600 L/h. The flow rate of the conical orifice was 50 L/h. RESULTS： The linear range of o-phenylenediamine，phenylacetic acid and dibasol hydrochlo- ride were 0.427-4.27 μg/mL（r＝0.998 9），0.403-4.03 μg/mL（r＝ 0.998 9）and 0.82-8.20 μg/mL（r＝0.999 9），respec-tively. The limits of quantitation were 0.042 7，0.134 3，0.088 7 μg/mL. The limits of detection were 0.021 4，0.067 1，0.044 3 μ g/mL. RSDs of precision ，stability，reproducibility and durability tests were all less than 2％. The average recoveries were 98.31％- 99.78％-102.23％ for phenylacetic acid （RSD＝0.70％，n＝9）. No o-phenylenediamine was detected in 6 batches of dibazol hydrochloride raw materials ；the contents of phenylacetic acid · were 0-0.04％ ；the contents of maximum unknown impurity were 0.05％ -0.25％ ；total contents of unknown impurity were 0.05％-0.31％. In 77 batches of Dibasol hydrochloride tablets ，the contents of o-phenylenediamine were 0-0.11％，the contents of phenylacetic acid were 0-0.03％；the contents of maximum unknown impurity were 0.06％-0.51％；total contents of unknown impurity were 0.10％-0.62％. It was speculated that maximum unknown impurity was 2-（hydroxyphenylmethyl）benzimidazole （hydrobenzde）. CONCLUSIONS ：Established method is rapid ，accurate and specific ，and can be used for the determination of related substances in dibasol hydrochloride raw materials and tablets. The maximum unknown impurity may be benzimidazoles.
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We have developed a new method using HPLC-CAD (charged aerosol detector) for the quantitative analysis of cyclovirobuxine D and related substances in the API of Huangyangning tablets. The related substances were further studied by HPLC-Q-Exactive coupled with hybrid quadrupole-orbitrap mass spectrometry. A HILIC column of XBridge Amide (4.6 mm×250 mm, 5 μm) was used, and the mobile phase was composed of acetonitrile and 100 mmol·L-1 ammonium formate (85∶15), which was adjusted to pH 2.8 with formic acid. Isocratic mode elution was adopted at a flow rate of 1.1 mL·min-1. The column temperature was set at 30 ℃. For CAD, the temperature of atomization and gas pressure were respectively set at 35 ℃ and 62.2 psi. This method detected and quantified five related substances to cyclovirobuxine D. The results showed that the LOD and LOQ of cyclovirobuxine D was 12.588 ng and 28.323 ng, respectively with an average recovery of 95.74% (RSD = 1.79%, n = 6). The content of cyclovirobuxine D in 12 batches of API samples provided by three manufacturers was from 79.94% to 88.49%, with an average value of 82.20%. The total content of the five related substances was from 15.99% to 22.15% with an average value of 20.10%, using an external standard method with cyclovirobuxine D as the reference and according to the CAD uniform response to non-volatile substances. The newly developed HPLC-CAD method has advantages in terms of the comprehensiveness of signals from Buxus alkaloids without UV absorption and with high sensitivity to its trace-related substances; the method yields good separation between the components and is compatible with mass spectrometry. It is applicable for the accurate quantitative analysis of main components and related substances in the API of Huangyangning tablets.
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@#A novel method was developed for the content assay and related substances determination of neomycin sulfate by high performance liquid chromatography combined with pulsed amperometric detection(HPLC-PAD). The HPLC was performed on Thermo AcclaimTMAmG C18(4. 6 mm×150 mm, 3 μm). The mobile phase consisted of aqueous solution with 2% trifluoroacetic acid containing 0. 01% pentafluoropropionic acid and 0. 6%NaOH. The pulsed amperometric detector was operated with aquadruple-potential waveform for the detection. Neomycin B, Neomycin C and thirteen related substances were adequately separated by the established HPLC conditions. The limits of detection(LOD)and quantification(LOQ)of neomycin B and neomycin C were both 1. 75 ng and 3. 5 ng, respectively. Good linearities of neomycin B and neomycin C were found in their respective ranges which their correlation coefficients were greater than 0. 998 5. The established method is characterized by high specificity, sensitivity and wide range of linearity which has a good application prospect and provides the basis for improving the standard and quality control of neomycin sulfate.
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OBJECTIVE: To establish an HPLC method combined with pulsed amperometric detection for the analysis of ribostamycin sulfate and related substance. METHODS: The HPLC was performed on Thermo AcclaimTMAmG C18 column (4.6 mm×150 mm,3 μm). The mobile phase consisted of acetonitrile and 0.2%(V/V) pentafluoropropionic acid aqueous solution containing 0.15%(V/V) trifluoroacetic acid (1∶99, V/V). The pH of the aqueous solution was adjusted to 1.5 with 50%(m/m) sodium hydroxide solution. The pulsed amperometricdetector was operated with aquadruple-potential wave form at 35 ℃ and the injection volume was 25 μL. RESULTS: Ribostamycin and its related substances were adequately separated under the established HPLC conditions. The LOD and LOQ of ribostamycin were 0.15 μg•mL-1(3.75 ng injected) and 0.375 μg•mL-1(9.38 ng injected), respectively. The linearity of ribostamycin ranged from 0.15 to 40.0 μg•mL-1 with a correlation coefficient of 0.999 3.The repeatability RSDs(n=6)for method validation of the content assay and total impurities test were 0.33% and 1.10%, respectively. CONCLUSION: The established method is characterized by high specificity, sensitivity and good stability. The established method has much lower test cost than the current Ch.P 2015 method and is hopeful to replace it.
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Objective: To establish a method for the determination of related substances in dexmetomidine hy- drochloride gels,and investigate the compatibility of dexmedetomidine hydrochloride and excipients in the dexmetomi- dine hydrochloride gels. Methods: HPLC was performed on an octadecylsilane bonded silica gel column by a gradient elution with acetonitrile/0.008 mol/L NaH2PO4 solution as mobile phase. Flow rate was 1.0 ml/min. Column temperature was 30℃. Injection volume was 50 μl. Detection wavelength was 210 nm. According to the Basic Technical Guidelines for the Research of Chemical Drug Preparations,dexmetomidine hydrochloride was mixed with excipients in a certain propor- tion,and the mixtures were treated as test sample at the conditions of high temperature(60℃)and strong light(4500± 500)Lx irradiation. Sampling was performed on the 0,10th and 30th day of treatment,respectively. The appearance of the test samples was examined,and related substances in the samples were determined by the established HPLC method. Results: The established HPLC method showed a good specificity and durability,which could be used to accurately and effectively determine the changes of related substances. The appearance of the test samples the mixtures of dexmetomi- dine hydrochloride and excipients showed no changes in the full course of treatment at the tested conditions,and the re- lated substances were also not increased under the same conditions. Conclusion: The selected excipients(HPMC,pro- pylene glycol,methylparaben,sodium benzoate,and benzyl alcohol)all showed a good compatibility with dexmetomi- dine hydrochloride,and the tested mixture samples with the excipients and dexmetomidine hydrochloride were stable un- der the conditions of high temperature and strong light irradiation. These excipients could be used for the formulation screening for the dexmedetomidine hydrochloride gel development.
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OBJECTIVE： To establish method for simultaneous determination of 7 related substances in solifenacin succinate raw material. METHODS： HPLC method was adopted. The determination was performed on Thermo Hypersil ODS C18 column with mobile phase consisted of 0.02 mol/L KH2PO4 （0.02％ triethylamine， pH＝3.0）-acetonitrile （gradient elution） at the flow rate of 1.2 mL/min. The detection wavelength was set at 210 nm， and column temperature was 40 ℃. The sample size was 20 μL. The regression equation of solifenacin succinate and impurity A， C， D， I， J， K， L were drawn. Correction factors of impurities to solifenacin succinate were calculated with slope. The contents of impurities A， C， D， I， J， K and L were determined in 3 batches of solifenacin succinate raw material. RESULTS： The linear ranges of impurity A， C， D， I， J， K and L were 0.148 1-0.740 3， 0.142 9-0.714 5， 0.141 1-0.705 6， 0.148 9-0.744 6， 0.152 0-0.759 9， 0.137 9-0.689 6， 0.020 0-0.100 0 μg/mL （r＝0.999 8， 0.999 9 or 1.000 0）， respectively. The relative correction factors were 0.51， 0.40， 0.41， 0.91， 0.47， 0.85， 1.23. The limits of detection were 0.049 3， 0.047 6， 0.047 0， 0.048 1， 0.050 7， 0.046 0， 0.006 7 μg/mL. The quantification limits were 0.148 1， 0.142 9， 0.141 1， 0.148 9， 0.152 0， 0.137 9， 0.020 0 μg/mL， respectively. RSDs of precision， stability （24 h） and reproducibility tests were all lower than 5.0％ （n＝6）. Average recoveries were 101.09％， 97.58％， 93.77％， 98.56％， 99.68％， 97.07％ and 93.54％； RSDs were 0.75％ ， 0.51％， 0.47％， 0.84％， 0.70％， 0.75％， 1.21％ （n＝9）. The contents of impurity I in 3 batches of solifenacin succinate raw material were 0.015％-0.018％， other impurities were not detected. CONCLUSIONS： The method is sensitive， accurate and reliable， which can be used to determine the related substances of solifenacin succinate raw material.
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Objective: To establish an HPLC method for the determination of the related substances in edaravone and sodium chlo-ride injection. Methods: The column was Kromasil C18(250 mm×4. 6 mm, 5 μm) at the temperature of 30℃. The mobile phase A for gradient elution was a solution containing 0. 2% acetic acid and 0. 2% trimethylamine, and methanol was used as the mobile phase B. The flow rate was 0. 8 ml·min-1, the detection wavelength was 244 nm, and the injection volume was 20 μl. Results: Under the described chromatographic conditions, edaravone was completely separated from its impurities. Edaravone and its impurities had good linear relationships within the range of 0.1 μg·ml-1-3 μg·ml-1(r >0.998). The average recoveries ranged from 90.0% to 110. 0% (RSD<10% , n=9), and the contents of their related substances were all below the limits (0. 3% ). Conclusion: The method is accurate, simple and convenient, which can be used for the determination of the related substances in edaravone and sodium chloride injection.
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OBJECTIVE:To establish a method for the determination of related substances in Cabazitaxel injection. METHODS:HPLC method was used. The determination was performed on Agilent Eclipse XDB-C18column with mobile phase consisted of water-acetonitrile-ethanol(gradient elution)at the flow rate of 1.0 mL/min. The column temperature was 35 ℃,and the detection wavelength was set at 230 nm. The sample size was 20 μ L. Established method was used to determine related substances in 3 batches of Cabazitaxel injection. RESULTS:The linear relationship of cabazitaxel were 0.039-11.60 μ g/mL(r=0.999 8,n=7). The detection limit was 2×10-4μg,and quantitation limit was 8×10-4μg. RSD of precision and reproducibility tests were all lower than 10.0%(n=6). The amount of single impurity in 3 batches of samples ranged 0.07%-0.08%,and total amount of impurities were 0.26%-0.29%. CONCLUSIONS:Established method is simple,accurate and reliable,can be used for the determination of related substances in Cabazitaxel injection.
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To systematically identify the related substances in the original materials of breviscapine injection, 18 batches of samples collected from different pharmaceutical companies, its ethanol extract and breviscapine mother liquor concentrate were analyzed by high performance liquid chromatography (HPLC), and their structures were identified by ultra performance liquid chromatography and quadruple/time-of-flight mass spectrometry (UPLC-QTOF-MS). Under the selected chromatographic conditions, scutellarin and related substances have good resolution and 13 related substances were observed. Based on the molecular weight and fragmentation patterns obtained by UPLC-QTOF-MS as well as reference substances, their structures were elucidated as 6-hydroxyapigenin-6--glucosyl-7--glucuronide (1), 5,7,8,3',4',5'-hexahydroxyflavone-7--glucuronide (2), 5,6,7,3',4'-pentahydroxyflavone-7--glucuronide（3）and its isomer (4), patuletin-3--glucuronide (5), methoxylscutellarin (6), apigenin 7--glucuronide (7), isorhamnetin 7--glucuronide (8), diosmetin 7--glucuronide (9), scutellarein (10), scutellarin methyl ester (11), scutellarin ethyl ester (12), and apigenin (13). This study has clarified related substances in the original materials of breviscapine injection, providing references for the improvement of quality control for breviscapine drug material and its preparations.
ABSTRACT
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 μm), 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 μL. 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.