Study on Related Substances of Glucosamine Hydrochloride in Glucosamine Indometacin Enteric-Coated Tablets
Objective To establish a high-performance liquid chromatography(HPLC)method for the determination of related substances of glucosamine hydrochloride in Glucosamine Indometacin Enteric-Coated Tablets,and to analyze their influencing factors.Methods The chromatographic column was the NanoChrom ChromCore AQ C18 column(250 mm×4.6 mm,3 µm),the mobile phase was water-acetonitrile(gradient elution),the flow rate was 1.0 mL/min,the detection wavelength was 280 nm,the column temperature was 30℃,and the injection volume was 20 µL.The accelerated stability test and excipient compatibility test were used to analyze the influencing factors of related substances based on the production process.Results The linear ranges of known impurities including fructosazine,2,5-deoxyfructosazine,pyrazine,5-hydroxymethylfurfural,furfural,2-methylpyrazine,pyrrole-2-carboxaldehyde,5-methylfurfural were 0.20-3.30 µg/mL,0.20-3.00 µg/mL,0.25-7.54 µg/mL,0.18-7.04 µg/mL,0.25-10.10 µg/mL,0.25-10.18 µg/mL,0.25-10.17 µg/mL,0.26-10.50 µg/mL(R2≥0.999)respectively.The limit of detection was in the range of 0.3-5.0 µg/mL,the limit of quantification was in the range of 0.7-20.1 µg/mL.The RSDs of precision,stability,and repeatability tests were all lower than 2.0%.The average recovery rate of the above known impurities was in the range of 98.24%-101.20%,with RSDs in the range of 0.33%-2.19%(n=9).The factors that affected the generation of related substances in the formulation were process,temperature,and time;the factors that affected the growth rate of related substance content included process,excipients(mainly sodium hydroxymethyl starch)and moisture.Conclusion This method is simple,accurate,and specific,which can be used for the detection of related substances of glucosamine hydrochloride in Glucosamine Indometacin Enteric-Coated Tablets.We should optimize the drying temperature and time in the process,improve the rationality of adding excipients,and control the moisture in the tablets to further improve the uniformity and stability of the formulation quality.
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