离子色谱法测定注射用酒石酸吉他霉素中酒石酸含量及成盐率合理性评价

Determination of Tartaric Acid in Kitasamycin Tartrate for Injection by Ion Chromatography and the Evaluation of the Salt-forming Rate

关键词:  离子色谱法  酒石酸  pH值  澄清度

Key words:  ion chromatography  tartaric acid  pH value  clarity

摘要:

目的 建立离子色谱法测定注射用酒石酸吉他霉素中酒石酸含量，通过酒石酸成盐率与pH值、澄清度的相关性研究，评价样品成盐率的合理性。方法 离子色谱法采用IonPac AS19阴离子交换色谱柱（4.0 mm×250 mm，7.5 μm）和IonPac AS19保护柱（4.0 mm×50 mm），检测器为抑制电导检测器，以20 mmol·L^-1氢氧化钾溶液为流动相，流速1.1 mL·min^-1。吉他霉素原料药与不同质量比的酒石酸进行配伍试验，探讨酒石酸比例与溶液pH值、澄清度的关系。结果 酒石酸浓度为1.0~50.0 μg·mL^-1，峰面积与其浓度呈良好的线性关系（r=0.999 8，n=6）；定量限为1.0 μg·mL^-1；平均回收率为99.5%（RSD=1.6%，n=9）。测定了2个厂家共10批样品，pH值4.2~4.3，酒石酸含量10.9%~11.4%，无显著统计学差异。配伍试验表明，溶液澄清时的酒石酸含量为8.8%~16.1%，溶液澄清时的pH范围为3.4~5.0。结论 本离子色谱法可用于注射用酒石酸吉他霉素中酒石酸含量的测定，2家企业的成盐工艺较为合理。

Abstract:

OBJECTIVE To establish an ion chromatography method for determination of tartaric acid in kitasamycin tartrate for injection, through the correlation study of tartaric acid salt-forming rate with pH value and clarity, evaluated the rationality of the salt-forming rate. METHODS The chromatographic separation was performed on an IonPac AS19 anion exchange column(4.0 mm×250 mm, 7.5 μm) and IonPac AS19 guard column(4.0 mm×50 mm), using suppressed conductivity detector. An isocratic eluent of 20 mmol·L^-1 KOH was chosen as mobile phase, flow rate was 1.1 mL·min^-1. Binary mixture of kitasamycin and tartaric acid prepared in different mass rations was performed to explore the possible correlation between the salt-forming rate and pH value and clarity. RESULTS A good linear relationship was observed within the range of 1.0-50.0 μg·mL^-1(r=0.999 8, n=6). The limit of quantification was 1.0 μg·mL^-1. The average spiked recovery was 99.5% at three concentration levels with RSD of 1.6%(n=9). Ten batches of samples from 2 manufactures were tested using this validated method, the percentage content of tartaric acid was between 10.9%-11.4%, and no significant difference was found between the samples from 2 manufactures. The pH value were all around 4.2-4.3. The compatibility test showed that the clarity of sample solution could only be achieved when the percentage content of tartaric acid was between 8.8% and 16.1%, meanwhile the pH value was around 3.4-5.0 under this condition. CONCLUSION This method is accurate and reliable to determine the content of tartaric acid in kitasamycin tartrate for injection. The salt-forming rate of kitasamycin and tartaric acid in the samples of kitasamycin tartrate for injection is reasonable and qualified.