| 第 52 卷第 6 期 |  | Vol. 52 No. 6 | | 2022 年 12 月 | Dec 2022 |
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所屬欄目：分析與測試
HPLC法測定阿伐那非中間體4-（3-氯-4-甲氧基芐胺基）-2-甲硫基-5-乙氧羰基嘧啶的有關(guān)物質(zhì) |
| 王 帆，楊 琪，李 帥，郭新艷，孫 清
（山東省藥學(xué)科學(xué)院 山東省生物藥物重點(diǎn)實(shí)驗室，山東 濟南 250101） |
| 摘 要：建立高效液相色譜法測定阿伐那非中間體4-（3-氯-4-甲氧基芐胺基）-2-甲硫基-5-乙氧羰基嘧啶（M-1）的有關(guān)物質(zhì)。以C18為填充物的不銹鋼柱及紫外檢測器，在254 nm波長(cháng)下，以0.02 mol/L磷酸二氫鉀水溶液（用1 mol/L氫氧化鉀溶液調節pH=5.5）-乙腈進(jìn)行梯度洗脫，以主成分自身對照法計算。M-1與4個(gè)已知雜質(zhì)均可達到基線(xiàn)分離，在各自濃度范圍內線(xiàn)性關(guān)系良好，精密度試驗的RSD均不大于2%，平均回收率99.16%~100.44%，RSD 0.69%~1.03%，檢測限0.020~0.15 µg/mL，定量限0.061~0.45 µg/mL。該方法操作簡(jiǎn)便，準確度、專(zhuān)屬性良好，可滿(mǎn)足中間體M-1的質(zhì)量控制要求。 |
| 關(guān)鍵詞：阿伐那非；中間體；有關(guān)物質(zhì)；高效液相色譜法 |
| 中圖分類(lèi)號：R977.1 文獻標識碼：A 文章編號：1009-9212（2022）06-0085-05 |
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| Determination of Related Substances in 4-(3-Chloro-4-methoxybenzylamino)-2-methylthio-5-ethoxycarbonyl pyrimidine as Intermediate of Avanafil by HPLC |
| WANG Fan, YANG Qi, LI Shuai, GUO Xin-yan, SUN Qing
(Shandong Academy of Pharmaceutical Sciences, Key Laboratory for Biological Drug Research of Shandong Province, Jinan 250101, China) |
| Abstract：To establish a HPLC method for the determination of related substances in 4-(3-chloro-4-methoxybenzylamino)-2-methylthio-5-ethoxycarbonyl pyrimidine (M-1) as an intermediate of Avanafil. The determination was performed on a C18 column and UV absorbance detector at a wavelength of 254 nm, 0.02 mol/L potassium dihydrogen phosphate solution (pH was adjusted to 5.5 with 1 mol/L potassium hydroxide solution) and acetonitrile were used as the gradient elution reagents. The principal component self-control comparison method was used to calculate the content of the impurities. M-1 and four known impurities could achieve a baseline separation, and the linear relationship was good within their respective concentration ranges; RSD of precision test was no more than 2%, the average recovery rate was 99.16%~100.44%; and the RSD was 0.69%~1.03%; the limit of detection was 0.020~0.15 μg/mL; the limit of quantification was 0.061~0.45 μg/mL. This method was accurate, specific, simple and easy to operate, which was suitable for the quality control of the M-1. |
| Key words：Avanafil; intermediates; related substances; HPLC |
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基金項目：山東省重點(diǎn)研發(fā)計劃（重大科技創(chuàng )新工程項目）（2021ZDSYS07）。
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作者簡(jiǎn)介：王 帆（1986—），女，遼寧朝陽(yáng)人，主管藥師，碩士，研究方向：新藥研發(fā)（E-mail：sail-163@163.com）。
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收稿日期：2022-07-07
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