| 第 53 卷第 3 期 |  | Vol. 53 No. 3 | | 2023 年 6 月 | Jun 2023 |
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所屬欄目：分析與測試
HPLC檢測器聯(lián)用法測定瑞格列奈二甲雙胍片中瑞格列奈的有關(guān)物質(zhì) |
| 張 琳1，2，3，劉 林1，顏 紅1，邢雪敏1*，劉葵葵1，李 欣1
（1. 山東省藥學(xué)科學(xué)院 山東省化學(xué)藥物重點(diǎn)實(shí)驗室，山東 濟南 250101；2. 山東福瑞達醫藥集團有限公司，山東 濟南 250101；3. 山東省黏膜與皮膚給藥技術(shù)重點(diǎn)實(shí)驗室，山東 濟南 250101） |
| 摘 要：建立二極管陣列及熒光檢測器聯(lián)用的HPLC方法測定瑞格列奈二甲雙胍片中瑞格列奈的有關(guān)物質(zhì)。以辛烷基硅烷鍵合硅膠為填充劑，以磷酸二氫鉀緩沖溶液與乙腈為流動(dòng)相，采用梯度洗脫分離；檢測器為二極管陣列與熒光檢測器串聯(lián)，二極管陣列檢測器檢測波長(cháng)240 nm，熒光檢測器激發(fā)波長(cháng)244 nm、發(fā)射波長(cháng)348 nm；流速1.0 mL/min，進(jìn)樣體積50 μL，柱溫40 ℃。兩種檢測器條件下主峰及各雜質(zhì)之間分離度均較好；各雜質(zhì)及瑞格列奈檢測限分別為0.012、0.020、0.103、0.088、0.073、0.024 ng/mL，定量限依次為0.053、0.060、0.309、0.264、0.219、0.072 ng/mL；主峰及各雜質(zhì)在1~50 ng/mL濃度范圍內濃度與峰面積線(xiàn)性關(guān)系良好；五種雜質(zhì)的平均回收率為98.3%、94.2%、98.2%、96.5%、103.6%，RSD依次為3.8%、2.6%、4.1%、3.9%、5.6%（n=6）；6份樣品中，雜質(zhì)1平均含量為0.05%，RSD為6.8%，其他已知雜質(zhì)均未檢出，未知雜質(zhì)未檢出；供試品溶液在8 h內穩定性良好。該方法靈敏度高，準確度和重復性均較好，可用于檢測瑞格列奈二甲雙胍片中瑞格列奈的有關(guān)物質(zhì)。 |
| 關(guān)鍵詞：瑞格列奈二甲雙胍片；瑞格列奈；有關(guān)物質(zhì)；檢測器聯(lián)用法 |
| 中圖分類(lèi)號：O657.7 文獻標識碼：A 文章編號：1009-9212（2023）03-0068-05 |
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| Determine Repaglinide-related Substances in Repaglinide and Metformin Tablets Using HPLC with Combined Detectors |
| ZHANG Lin1,2,3, LIU Lin1, YAN Hong1, XING Xue-min1*, LIU Kui-kui1, LI Xin1
(1. Key Laboratory for Chemical Drugs Research of Shandong Province, Shandong Academy of Pharmaceutical Sciences, Ji’nan 250101, China; 2. Shandong Freda Pharmaceutical Group Co., Ltd., Ji’nan 250101, China; 3. Shandong Provincial Key Laboratory of Mucosa and Transdermal Drug Delivery Technology, Ji’nan 250101, China) |
| Abstract：The related substances of repaglinide in the repaglinide and metformin compound tablets were more accurately determined by HPLC method with diode array and fluorescence detector. Octylsilane-bonded silica gel was used as filler; potassium dihydrogen phosphate buffer solution and acetonitrile were taken as mobile phases, gradient elution was used for separation; the detector was a diode array connected in series with a fluorescence detector, which was used to detect the wavelength 240 nm. Besides, the excitation wavelength of the fluorescence detector is 244 nm; the emission wavelength is 348 nm; the flow rate was 1.0 mL/min；the injection volume was 50 μL; the column temperature was 40 ℃. The repaglinide and other impurities were well separated under the conditions of the two detectors. The limits of detection were 0.012, 0.020, 0.103, 0.088, 0.073, and 0.024 ng/mL, repectively and the limits of quantitation were 0.053, 0.060, 0.309, 0.264, 0.219, and 0.072 ng/mL, respectively. The main peak and each impurity had a good linear relationship between the concentration and the peak area in the concentration range of 1~50 ng/mL.The average recoveries of the 5 impurities were 98.3%, 94.2%, 98.2%, 96.5%, 103.6%. At the same time, the RSD were 3.8%, 2.6%, 4.1%, 3.9%, and 5.6% (n=6). The average content of impurity 1 in six smples was 0.05%, and the RSD was 6.8%. The stability of the test solution was good in the 8 h. This method has high sensitivity, good accuracy and repeatability. Therefore, it can be used to detect the related substances of repaglinide in repaglinide and metformin tablets. |
| Key words：repaglinide and metformin tablets; repaglinide; related substances; combination detector |
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作者簡(jiǎn)介：張 琳（1981—），女，山東濟南人，高級工程師，碩士，研究方向：藥物質(zhì)量控制（E-mail：25144123@qq.com）。
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聯(lián) 系 人：邢雪敏，工程師，研究方向：藥物質(zhì)量控制（E-mail：34692577@qq.com）。
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收稿日期：2023-03-27
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