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@#Using high performance liquid chromatography and high resolution orbital trap mass spectrometry, a two-dimensional online desalting detection method was established to determine the structure of the impurities detected under the official testing conditions of lansoprazole enteric solution preparation, and a chromatographic method compatible with mass spectrometry was established to determine and presume the structure of the impurities that could not be separated by the the official testing method.The identification of impurity was to presume its structure according to the presence of impurity reference product, so as to investigate the difference of impurity spectrum of products from different manufacturers.The one-dimensional chromatographic conditions for the 2D online desalting method were the same as those in China Pharmacopoeia (2020) under relevant substances.Two-dimensional chromatography was performed on a Waters C18 T3 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid in water-acetonitrile mobile phase and gradient elution.The chromatographic conditions for the compatible mass spectra were based on an Agilent Extend C18 (4.6 mm × 150 mm, 5 μm) column with mobile phase A: 25 mmol/L ammonium acetate and B: 25 mmol/L ammonium acetate-acetonitrile (1∶4) [pH adjusted to 6.5 with glacial acetic acid], with gradient elution. Nine impurities were detected by two-dimensional online desalting method, with 5 known impurities (A-E) and 4 unknown ones.14 impurities were detected by the compatible mass spectrometry method, with 9 unknown impurities (4 consistent with the results of two-dimensional online desalting method, and 5 newly detected).The structures and sources of the unknown impurities were deduced.The two detection methods of lansoprazole preparation by high-performance liquid chromatography-high resolution orbital trap mass spectrometry have guiding significance for quality control and process evaluation.
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Objective:To establish a method for the determination of omeprazole delayed release capsules and investigate the be-havior of reference preparations to provide experimental basis for generic drugs quality consistency evaluation. Methods:According to the first dissolution method (basket method) stated in 0. 931 of Chinese Pharmacopeia (2015 edition), the type of release media, solu-bility and stability of omeprazole in different media, effect of different treatment methods on the drug adsorption in the solution, differ-ent rotation speed and the methodology of ultraviolet spectrophotometry were investigated. Results:The rotation speed was 75 r·min-1 with the dissolution medium volume of 900 ml. The dissolution profiles of omeprazole delayed release capsules in three different media ( pH 6. 0 phosphate buffer, pH 6. 8 phosphate buffer and water containing 3% Tween-80) were determined with online filteration. The solubility of omeprazole in the different media was 0. 123, 0. 078 and 0. 275 mg·ml-1 , respectively. The results showed that ome-prazole was degraded 44%, 8% and 14% in 2 h in the above three release media, and degraded up to 43% in 6 h in water containing 3% Tween-80. The linear of omeprazole was 0. 209 4-20. 94, 0. 204 8-20. 48 and 0. 2016-20. 16 μg·ml-1 with the average recovery of 99.3% (RSD=0.7%,n=12), 99.7% (RSD=0.9%,n=12) and 99.5% (RSD=0.6%,n=12) respectively in the three media. Conclusion:The method is accurate and reliable, which can be used to study the quality consistency of omeprazole delayed re-lease capsules.
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Objective:To evaluate the quality of carbazochrome sodium sulfonate Injection from different manufacturers, analyze the existing problems and provide the reference for the improvement of clinical medication safety. Methods:Statutory testing methods and the exploratory research methods were used to examine the samples, and the quality status of carbazochrome sodium sulfonate Injec-tion was evaluated according to the results. Results:Totally 89 batches of the samples were tested by the current standard. The quali-fied rate was 97. 8%, and the two batches of unqualified samples were carbazochrome sodium sulfonate and sodium chloride Injection with unqualified insoluble particles. Overall, the quality risk of carbazochrome sodium sulfonate for injection was low, and the safety of carbazochrome sodium sulfonate and sodium chloride Injection needed further research. Conclusion:The quality of carbazochrome so-dium sulfonate Injection basically meets the current standard, and the exploratory research suggests that the current standard is imper-fect. It is urgent to improve the related substance detection in the standard and determine the reasonable limits for the degradation im-purities and the other impurities. The clinical medication safety of carbazochrome sodium sulfonate and sodium chloride Injection needs further research.
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<p><b>OBJECTIVE</b>To establish a HPLC method with the relative correction factors (RCFs) for quantification of five critical related substances (A, B, C, D and E) in puerarin and its injection.</p><p><b>METHOD</b>Taking puerarin as the internal standard, corresponding RCFs of the critical related substances were determined respectively. According to their RCFs, simultaneous determination of five related substances in puerarin and its injection was performed. The method was evaluated by comparison the quantitative results of external standard method and the method with RCFs correction.</p><p><b>RESULT</b>There were no significant differences in the results of five critical related substances in 38 batches of puerarin and its injection by external standard method and the method with RCFs correction.</p><p><b>CONCLUSION</b>The HPLC method with RCFs was validated to be accurate and can be successfully applied to determine the critical related substances in puerarin and its injection.</p>
Subject(s)
Humans , Chromatography, High Pressure Liquid , Methods , Reference Standards , Drug Contamination , Drug Stability , Hydrogen-Ion Concentration , Injections , Isoflavones , Pharmaceutical Solutions , Plant Extracts , Chemistry , Plants, Medicinal , Chemistry , Pueraria , Chemistry , Quality Control , Reproducibility of Results , Temperature , Vasodilator AgentsABSTRACT
An analysis of the medical risks exposure for resident doctors in their standardized training,and insights into the risk management measures proposed for this stage.These measures include:1) Pre-control of risks;2) Full-length supervisor of such training stage;3) Systematic education for medical risk exposure;4) Timely guidance on risk identification and response;5) Development of the evidence awareness.
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Combined effects of ?-chlorohydrin and glycidol on the ultrastructure of theinitial segment and the tail region of the rat epididymis have been studied by ultra-thin sections under electronmicroscope.Individual effects of the both drugs on thesame tissues were also examined simultaneously.The major results are as follows.1.Numbers of swollen and degenerated mitochondria were observed in principalcells,clear cells,apical cells and basal cells of epididymal epithelium,as well as insmooth muscle cells of the ductus epididymidis and in endothelial cells of the capil-laries in epididymal interstitium during a period of 3～30 days after administrationof low dose of ?-chlorohydrin combined with glycidol(5 mg ?-chlorohydrin plus75mg glycidol/kg/day?2),which previously has been proved to be effective inmale rat antifertility.Additionally,Golgi vacuoles,pinocytotic vesicles,multivesicularbodies,stereocilia and smooth endoplasmic reticulum in the apical cytoplasm of someprincipal cells occasionally were found to decrease in number.No Morphologicalchanges of the nuclei were found in these affected cells.The number of morphologi-cally unchanged mitochondria appears to become more with extended time after drugswithdrawal.2.In the group treated with the large combined dose of the drugs(20 mg ?-chlorohydrin plus 100 mg glycidol/kg/day?2),apart from the changes mentionedabove,necrosis and exfoliation of some epididymal epithelial cells could be found.Some lesions of the sperm,such as the destruction of the cytoplasmic membrane,swelling of mitochondria and pyknosis of nucleus were present in a few specimenstaken from this group.3.Effects similiar to that of the combined use of the drugs were also found ingroups using ?-chlorohydrin or glycidol alone,but a less degree of lesions revealed.These observations suggested that the antifertile effects of ?-chlorohydrin andglycidol either used in combination or alone could result injury of mitochondria inepididymal epithelial cells,which should lead to the decrease of the function ofepididymis,hence to interfere with the maturation of the sperm in it.
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A comparative observation about histological and histochemical study were made onthe preservating methods of local ischemic kidney of dogs.The methods of this exp-eriment were divided into five groups:A.Local hypothermia;B.Hypothermic perfu-sion solution 500ml,4℃,containing Procaine 450 mg and Heparin 100 mg,infusedinto renal artery;C.Hypothermic perfusion solution 500ml,4℃,containing 20% Ma-nniton 32ml,25% MgSO_4 0.36 ml,Heparin 100 ml,infused into renal artery;D.Localhypothermia and heparin 30 mg injected into the same vessel.E.Local room tem-perature.The specimens were taken from the kidneys of the experimental dogs atvarious period after treated with every method.The results were as follows;A,D and E group presented irreversible histological changes within 4 hoursaftertreatment.Four hours later,the reaction of SDH,ATPase,AlPase werenegative.It suggested that the kidney damage was serious,as well as expressed thatthe effect of these preservating methods for ischemic kidney are not satisfactory.In B group,the histological and histochemical alteration is very light and almostreversible,during 60 days after treatment.In C group,hypothermic perfusionsolution containing Mannitol,MgSO_4 etc either during experiment or follow observa-tion for 60 days,no histological and histochemical alterations were found.It indica-ted that this method is an ideal perservating technique for ischemic kidney.
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It was reported that a complete antifertility action of alpha-chlorohydrin in combination with glycidol in male rats after a daily oral dose of 5mg/kg and 75mg/kg respectively for two days. Simultaneously some ultrastructural changes including mitochondrial swelling, atrophy of Golgi complex, decreasing in pinocytotic vesicles and stereocilia were found in principal cells of epididymis within 3 days after medication.In this experiment the animals received 3, 6 and 9 courses of treatment respectively, each course included two days of administration with a daily dose mentioned above and eight days of cessation of medication.The specimens of initial segment of epididymis, liver and kidney were taken at the end of 3 rd, 6 th and 9th courses of treatment for electron microscopy.The principal cells of initial segment of epididymis revealed a normal feature at the end of 3 rd and 9 th course of treatment. But at the end of 6 th course of treatment, the atrophy of Golgi complex and the decrease in stereocilia and pinocytotic vesicles were found in some principal cells.Any ultrastructural changs of sperms in the initial segment were not found by electron microscope.There was also mitochondrial changes with striking increase in the density of the matrix and reduction of size in some liver cells at the end of 6 th course of treatment, but not at the end of 3 rd or 9 th course of treatment. The epithelial cells of nephron in all the specimens revealed a normal ultrastructural feature.The results suggest that the ultrastructural changes of the principal cells and the liver cells induced by the mixture of the drugs could be recovered at the end of treatments.