丹参滴注液清洁验证检验方法的确认研究

Verification of cleaning validation test method for salvia infusion solution

目的建立丹参滴注液清洁方法，对清洁残留检验方法进行验证确认。方法丹参滴注液生产结束后清洁剂为1％氢氧化钠溶液、1％枸橼酸溶液和注射用水，清洁后残留物限度≤10mg·L^-1，棉签擦拭取样，采用HPLC测定丹参素钠和原儿茶醛的残留量，色谱柱为C18柱（250mm×4．6mm，5μm），流动相为甲醇-0．5％冰醋酸溶液（5：95），流速1．0mL·min^-1。结果丹参素钠和原儿茶醛在下述范围内与峰面积呈良好的线性：（I）5．456～27．898mg·L^-1（r=0．9999）、（Ⅱ）0．530～2．684mg·L^-1（r=0．9999）。精密度和准确度在设定范围。结论丹参滴注液清洁方式可行，清洁效果确切，残留活性成分检测准确、灵敏，通过确认证明该检验方法可用于丹参滴注液清洁验证残留活性成分的检测。

Objective To establish a cleaning validation test method for salvia infusion solution,and to verify the cleaning residue test method. Methods The cleansers used after the production of salvia infusion solution were 1% sodium hydroxide solution, 1% citric acid solution and water for injection. The residue limitation after cleaning was no more than 10 mg · L^-1. Swab was used to take samples by wiping, and the residue of tanshinol sodium and protocatechualdehyde was measured by HPLC. The chromatographic column was C18 column （ 250mm×4.6mm,5μm） , the flowing phase was methanol - 0.5 % glacial acetic acid solution （ 5 ： 95 ） , and the flow velocity was 1.0 ml ·min ^-1. Results Tanshinol sodium and protocatechualdehyde were well linearly correlated with peak area in the following ranges ： （ Ⅰ ） 5. 456 - 27. 898 mg· L^-1 （ r = 0. 999 9） , （Ⅱ ） 0.530 - 2. 684 mg · L^-1 （ r = 0.999 9 ）. Precision and accuracy were in the setting range. Conclusions The cleaning method for salvia infusion solution is feasible, the cleaning effect is impressive, the test of residual active ingredients is accurate and sensitive. By verification, we have proved that this test method can be used in the cleaning validation test of residual active ingredients in salvia infusion solution.