1.Comparison of the Quality of Generic and Original Preparations of Thioctic Acid Injection and Study on Its Acute Toxicity Test in Mice
Yuan TIAN ; Dezhi KONG ; Ziqi LIU ; Saihang ZHANG ; Leiming REN
China Pharmacy 2019;30(19):2618-2623
OBJECTIVE: To compare the quality of original preparations of Thioctic acid injection and generic preparations from 2 domestic manufacturers, discuss the acute toxicity test of mice and to investigate the project of consistency evaluation methods. METHODS: According to the quality standard that stated in Chinese Pharmacopeia, physicochemical properties (characters, pH, osmotic pressure, etc., contents and related substances of samples of Thioctic acid injection as well as LD50 in acute toxicity test (n=10), and mortality of mice after administration of injection solution (n=30) were compared among 3 manufacturers. RESULTS: The physicochemical properties as and related substances of the original drug and 2 generic drugs were all in line with the quality standard; the contents of 3 samples ranged 95%-105%. The acute toxicity test results showed that the LD50 values of 2 generic drugs (LD50: 247.911 mg/kg, 95% confidence interval: 222.209-277.999 mg/kg;LD50: 215.291 mg/kg, 95% confidence interval: 196.637-235.053 mg/kg) were smaller than that of original drug (LD50: 266.534 mg/kg, 95% confidence interval: 250.597-283.418 mg/kg), but there was no statistical difference (P>0.05). The results of 3 repeated experiments showed that there was statistical significance in the number of animal death caused by the 2 generic drugs (26, 28) was more than that of the original drug (19) (all P<0.05), when injection solution was injected into mice in a single dose. After administration of the original drug, mice showed excitatory reactions such as movement and squeal, while 2 generic drugs showed inhibitory reactions. CONCLUSIONS: 2 generic drugs of Thioctic acid injection and the original drug all conform to the relevant regulations of Chinese Pharmacopoeia in terms of preparation quality standards, but the results of acute toxicity test are quite different, so it is difficult to prove the consistency between the 2 generic drugs and the original drug. Therefore, acute toxicity test is necessary for the consistency evaluation of injections.