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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 study the dose-time-toxicity relationship of hepatotoxicity in mice with multiple administration of Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning capsules (CQC).Methods Mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium,and low dose groups.The acetaminophen contents of high,medium,and low doses were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH groups,and the doses of CQC group were 1437.70,2300.31,and 3 680.50 mg/kg,ig administration,once daily for 5 d.General state and toxicity of mice were observed.The changes of ALT,AST,AKP,TBIL,and ALB levels in serum and organ indexes of liver,spleen,thymus,and kidney were tested on day 1,3,7,11,and 14 after multiple administration.Results CQC with the dosage range of 1 437.70-3 680.50 mg/kg to mice within 14 d,has not yet induced the increase of AST,ALT,AKP,TBIL,and ALB levels and changes of organ indexes of liver,thymus spleen,and kidney compared with normal control (P ＞ 0.05).PT,CPAH,and CDH with repeated dose of 425.98-681.57 mg/kg could induce significant increase of the levels ofALT,AST,AKP,and TBIL which reached the peak on day 1 (P ＜ 0.05),and then gradually decreased on day 3-14.The level of ALB significant decreased on day 1-11 (P ＜ 0.05),and then gradually recovered on day 11-14.The liver index significant increased on day 1-3 (P ＜ 0.05),and recovered on day 7-14.Conclusion Multiple administration of CQC could not induce liver injury in mice within 14 d,while multiple administration ofPT,CPAH,and CDH could induce hepatotocixity in mice with a certain dose,and show an obvious dose-time-toxicity relationship.
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Objective To study the time-toxicity and dose-toxicity relationship of hepatotoxicity induced by Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning Capsules (CQC) with single dose in mice.Methods In the Time-Toxicity relationship study,Kunming mice were randomly divided into control,PT,CPAH,CDH,and CQC group,and mice of.each drug administration group were randomly divided into nine subgroups according to the time (1,2,4,8,12,24,48,72 and 96 h after administration) of blood collection.The acetaminophen contents in PT,CPAH,and CDH groups were 425.98 mg/kg,and the dose of CQC group was 3 680.50 mg/kg.In the Dosage-Time relationship study,mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium and low dose group.The acetaminophen contents of high,medium,and low dose were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH group,and the dose of CQC group was 1437.70,2300.31,and 3680.50 mg/kg,10 mice in each group,sex in half.Blood was collected 12 h after administration.Animal behavior was observed every day,blood and organs were collected at the corresponding time points,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP) level were detected,and the organs index of spleen and thymus,liver were calculated.Results There were no significant changes of ALT,AST,ALP,and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice.The study on time-toxicity relationship indicated that,after once administration of PT,CPAH,and CDH at 425.98 mg/kg,mice showed toxic symptom such as hypokinesia,dry hair and so on,12 h was the most obvious,24 ～ 72 h disappeared.The level of ALT,AST,and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72,24,and 24 h in PT,CPAH,and CDH group.Their organ index of liver,spleen and thymus all had no significant changes.The study on the dosage-toxicity relationship indicated that,there were no significant changes of animal behavior,ALT,AST,ALP,and organs index after once ig administration of PT,CPAH,and CDH at 266.24 mg/kg.Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT,AST,and ALP increased significantly with the increase of dosage.Their liver index increased significantly with dosage of 681.57 mg/kg,but the organs index of spleen,thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice.Mice were once ig administration ofPT,CPAH,and CDH with a large dose,may induce acute liver injury and show obvious time-toxicity and dose-toxicity relationships.
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Objective To study the antipyretic effect of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules on the fever model induced by LPS and dry yeast in rats.Methods Fever was induced by ip injecting LPS (100 μg/kg) or sc injecting dry yeast (20％) in rats.We observed the changes of temperature of the rats after administration of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets (the acetaminophen contents were 205.67,102.83,and 51.42 mg/kg)and Chaiqin Qingning Capsules (1110.60,555.30,and 277.65 mg/kg).Maximum temperature rise height (△T) and temperature response index (TRI) were calculated,and the curve of average rise in temperature was drawn.Results Each dose group of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules had obvious antipyretic effect on the fever model induced by LPS and dry yeast in rats,and there was a certain dose-effect relationship.Conclusion Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules has certain antipyretic effect on LPS and dry yeast fever model in rats,and on the whole,the Western medicine acts rapid but continue for a short time,while the traditional Chinese medicine acts slow but continues for a long time.
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Objective:To evaluate the measurement uncertainty in the determination of paracetamol tablets by UV. Methods:The mathematical model of content determination by UV was established and the uncertainty sources were analyzed. Each active component of uncertainty was calculated, and the expanded uncertainty was obtained. Results:The expanded uncertainty for the UV determination of paracetamol tablets was 1. 2%,and the content determination result was (97. 0 ± 1. 2) % (k=2). Conclusion:The main sources of uncertainty are analyzed, which can provide reliable theoretical basis for the effective control of the method.
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The aim of this work was to explore the possibility of utilizing BFI as a tool for classifying, grouping and ranking binders based on performance in ameliorating capping and lamination in paracetamol tablets. Binders from different origins (starches, celluloses, natural gums, and synthetic gums) were used via wet granulation at concentrations ranging from 1.0 - 12.5% w/w to make paracetamol tablets with and without centre holes at a compression pressure of 7.5 arbitrary units. Requisite quality control tests were conducted on the tablets. The BFI values of the tablets were computed and statistically analyzed using Friedman’s test and regression analysis. The analyses revealed significant differences between the BFI values of the formulations (p < 0.05), projected BFI as a useful tool in grouping and ranking binders based on effectiveness in ameliorating capping and lamination in paracetamol tablets, but failed to be useful in classifying the binders based on nature or origin. Furthermore, with the exception of some of the tablets formulated with the celluloses or starches, others met the official requirements for good quality and those formulated with plant gums or PVP released up to 70% of drug in 15min at low binder concentrations. The present findings may serve as a guide to formulators since they may enable quick and easy selection of the best and most economic binder(s) from an array of available binders for the conversion of paracetamol or related powders into good quality tablets.
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OBJECTIVE:To establish a HPLC method for the determination of paracetamol,caffeine and aspirin in compound paracetamol tablets.METHODS:The chromatographic column was ODS,the mobile phase was methanol-4.2% glacial acetic acid solution(3∶7)with a flow rate at1.0ml/min;the detecting wavelength was 275nm,the sample size was 20?l and the column temperature was 25℃.RESULTS:The linear ranges of paracetamol,caffeine and aspirin were 16.08～428.80?g/ml(r=0.9981),3.42～91.20?g/ml(r=0.9988) and 23.87～769.92?g/ml(r=0.9999) respectively;The average recovery were 99.2%(RSD=0.23%),100.4%(RSD=0.63%)and 99.3%(RSD=0.11%)respectively.CONCLUSION:This method was simple,fast and accurate,which can be used for the content determination of compound paracetamol tablets.