冰点下降法测定注射用胸腺肽的渗透压

Determination of osmotic pressure of thymosin for injection by cryoscopy

目的采用冰点下降法测定注射用胸腺肽的渗透压,并观察其稳定性。方法用制备的0.9%NaCl和5%葡萄糖标准溶液对渗透压摩尔测定仪进行标定后,连续测定5次注射用胸腺肽的渗透压,计算变异系数(CV),验证该方法的精密度;取20批注射用胸腺肽,每瓶分别用500 ml和125 ml 0.9%NaCl溶液及5%葡萄糖溶液稀释,测定其渗透压;将注射用胸腺肽分别置(6±2)℃放置12个月,(25±2)℃放置6个月,分别于不同时间取样,稀释后测定渗透压,观察其长期和加速稳定性。结果 5次测得的注射用胸腺肽渗透压的变异系数为0.401%。20批注射用胸腺肽的渗透压在287～347 mOsmol/kg之间,以不同体积的0.9%NaCl和5%葡萄糖稀释样品后测得的渗透压的变异系数均较小,表明样品的渗透压批间差异较小;在稀释液量相同的条件下,5%葡萄糖试验组的渗透压显著高于0.9%NaCl组(P均<0.001)。注射用胸腺肽分别于(6±2)℃下放置12个月和(25±2)℃、相对湿度(60±10)%的条件下放置6个月,其渗透压均无显著变化。结论冰点下降法操作简便、快速,精密度高,可用于注射用胸腺肽渗透压的检测。

Objective To determine the osmotic pressure of thymosin for injection by cryoscopy and observe its stability. Methods Osmotic pressure meter was calibrated with prepared 0. 9% sodium chloride and 5% glucose standard solution, by which the osmotic pressure of thymosin for injection was determined for 5 times. The coefficient of variation（CV） of determination results was calculated, based on which the method was verified for precision. Twenty batches of thymosin for injection were diluted with 500 and 125 ml of 0. 9% sodium chloride and 5% glucose solution separately and determined for osmotic pressure. Three batches of tbymosin for injection were stored at（6 ± 2）℃ for 12 months and at（25 ± 2）℃ for 6 months separately, from which samples were taken at various time points, diluted and determined for osmotic pressure, of which the long-term and accelerated stabilities were evaluated. Results The CV of determination results of osmotic pressure of thymosin for injection was 0. 401%. The osmotic pressures of twenty batches of thymosin were 287 ± 347 mOsmol/kg, of which the CV was low after dilution with 0. 9% sodium chloride and 5% glucose at various volumes, indicating insignificant difference between various batches. However, the osmotic pressures of thymosin diluted with 5% glucose solution were significantly higher than those with 0. 9% sodium chloride at the same volume （each P 〈 0. 001 ）. No significant changes were observed in the osmotic pressures of thymosin after storage at （6 ± 2）℃ for 12 months and at a temperature of （25 ± 2）℃ and a relative humidity of （60 ± 10）% for 6 months. Conclusion Cryoscopy was simple, rapid and precise, which might be used for determination of osmotic pressure of thymosin for injection.