Study on the standard method for biological safety inspection of L-ornithine L-aspartate active pharmaceutical ingredients
OBJECTIVE To establish a standard method for biosafety test of L-omithine L-aspartate active pharmaceutical ingredients(OAAPI).METHODS According to the General rules of Chinese Pharmacopoeia(2020 edition),three biosafety tests including abnormal toxicity,vasopressor substance and depressor substance were conducted,and the limits were set.Related items were checked and verified for three batches of OAAPI.RESULTS 1/4 of the lower LD50 confidence limits of the three batches of OAAPI were 754.7 mg·kg-1,752.0 mg·kg-1 and 747.7 mg·kg-1,respectively.Consequently the limit was set as 30 mg·mL-1 in the abnormal toxicity test according to 25 mg·kg-1.Antihypertensive level caused by three batches of OAAPI at the doses of 333 mg·kg-1 and 267 mg·kg-1 did not exceed 1/2 of that caused by 0.1 μg·kg-1 of histamine phosphate,which was in line with the specified range.Consequently 267 mg·mL-1 was recommended as the limit in the test of depressor substance.The vasopressor value caused by three batches of OAAPI at the doses of 67 mg·kg-1 was all smaller than those caused by standard(0.45 IU·kg-1),and nearly half of those caused by standard(0.45 IU·kg-1).Consequently 67 mg·kg-1,which was 1/5 of the clinical dose of L-omithine L-aspartate,was recommended as the limit in the test of vasopressor substance.According to this standard,three batches of OAAPI in these biosafety tests all met the requirements.CONCLUSION The method can be used for the detection of abnormal toxicity,vasopressor substance and depressor substance of OAAPI.
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