[關(guān)鍵詞]
[摘要]
目的 建立唑來膦酸原料藥中雜質(zhì)A、B、C、D的HPLC測定方法。方法 采用Titank Phenyl-Hexyl色譜柱(250 mm×4.6 mm,5 μm)對雜質(zhì)A、B、C、D進行定量分析,以8 mg·mL-1的1-辛烷磺酸鈉和0.037 mg·mL-1的EDTA-二鈉為緩沖液,緩沖液-乙腈(4∶96)為流動相,進行等度洗脫,體積流量為0.8 mL·min-1,檢測波長為215 mm,柱溫為20℃,進樣量為10 μL。結(jié)果 空白溶液不干擾對各雜質(zhì)的檢測;各雜質(zhì)在相應(yīng)濃度范圍內(nèi)線性關(guān)系良好,R2均不小于0.990;各雜質(zhì)的檢測限分別為192.6、545.5、126.0、150.0 ng·mL-1,定量限分別為629、1 515、315、500 ng·mL-1;各雜質(zhì)的平均回收率分別為95.4%、82.4%、92.0%、95.9%,RSD分別為2.8%、2.7%、2.9%、2.4%;3批樣品有關(guān)物質(zhì)的測定結(jié)果顯示,各雜質(zhì)的質(zhì)量分數(shù)均低于0.3%。結(jié)論 方法學(xué)驗證結(jié)果顯示,建立的HPLC法適用于唑來膦酸原料藥中雜質(zhì)A、B、C、D的檢測。
[Key word]
[Abstract]
Objective To establish a HPLC method for the determination of impurities A, B, C and D in zoledronic acid. Methods A Titank Phenyl-Hexyl column (250 mm × 4.6 mm, 5 μm) was used for quantitative analysis of impurities A, B, C and D. Using 8 mg·mL-1 sodium 1-octanesulfonic acid and 0.037 mg·mL-1 EDTA-disodium as buffer, buffer with acetonitrile (4:96) as mobile phase. The elution was carried out at a volume flow rate of 0.8 mL·min-1, the detection wavelength was 215 mm, the column temperature was 20 ℃, and the injection volume was 10 μL. Results The blank solution did not interfere with the detection of impurities. Each impurity had a good linear relationship in the corresponding concentration range, and the correlation coefficient R2 was not less than 0.990. The detection limits of the impurities were 192.6, 545.5, 126.0 and 150.0 ng·mL-1, respectively, and the limits of quantification were 629, 1 515, 315 and 500 ng·mL-1, respectively. The average recovery rates of each impurity were 95.4%, 82.4%, 92.0% and 95.9%, respectively, and the RSD were 2.8%, 2.7%, 2.9% and 2.4%, respectively. The results of three batches of samples showed that the content of each impurity was less than 0.3%. Conclusion The method can be used to detect impurities A, B, C and D in zoledronic acid raw materials.
[中圖分類號]
R932
[基金項目]
江蘇省產(chǎn)教融合一流課程《藥物分析》建設(shè)項目;江蘇海洋大學(xué)專業(yè)學(xué)位研究生課程《藥品質(zhì)量控制》案例庫建設(shè)項目(YJSZY202102);江蘇海洋大學(xué)2023年一流課程《藥物儀器分析》建設(shè)項目;連云港市政策引導(dǎo)產(chǎn)學(xué)研項目(CYX2202)