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伊沙匹隆有关物质的HPLC法检测*

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  • 1.临沂市人民医院,临沂 276003;
    2.鲁南制药集团股份有限公司,临沂 276000
第一作者 Tel:(0539)8037273;E-mail:383854564@qq.com
**Tel:(0539)8216010;E-mail:bxzf29@foxmail.com

修回日期: 2022-08-31

  网络出版日期: 2024-06-24

基金资助

*山东省医药卫生科技发展计划面上项目(202002040822);江苏省重点实验室开放课题(XZSYSKF2021033)

Detection of related substances of ixabepilone by HPLC*

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  • 1. Linyi People’s Hospital, Linyi 276003, China;
    2. Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China

Revised date: 2022-08-31

  Online published: 2024-06-24

摘要

目的: 建立HPLC法检测伊沙匹隆原料药7个有关物质(有关物质1~7)的方法,为伊沙匹隆的质量控制提供方法依据。方法: 采用Welch XB-C18色谱柱(250 mm×4.6 mm,3 μm),以乙腈-0.04 mol·L-1乙酸铵水溶液为流动相,梯度洗脱,流速1.0 mL·min-1,柱温25 ℃,检测波长249 nm,进样量10 μL。结果: 伊沙匹隆与其7个有关物质的色谱峰均能良好分离。有关物质1~7质量浓度在0.05~2 μg·mL-1范围内与相应的峰面积呈良好的线性关系(r≥0.999 5);定量限分别为0.025、0.033、0.043、0.036、0.036、0.108、0.032 μg·mL-1;平均加样回收率(n=9)分别为98.5%、98.3%、101.2%、100.3%、97.6%、101.0%和98.6%,RSD分别为2.3%、2.8%、3.3%、2.1%、2.6%、5.7%和3.6%。3批伊沙匹隆样品检测结果显示,已知杂质及其他最大单个杂质含量均<0.083%,杂质总含量<0.256%。结论: 本方法专属性强,准确度高,可用于伊沙匹隆原料药有关物质的测定,同时填补了国内外关于伊沙匹隆有关物质检测方法的空白。

本文引用格式

伏瑶, 刘松霞, 范彩霞, 彭纪铭, 晋敦青, 侯君 . 伊沙匹隆有关物质的HPLC法检测*[J]. 药物分析杂志, 2022 , 42(10) : 1801 -1807 . DOI: 10.16155/j.0254-1793.2022.10.13

Abstract

Objective: To establish a detection method for the seven related substances (related substances 1-7) of ixabepilone API by HPLC and provide a method basis for the quality control of ixabepilone. Methods: Welch XB-C18 column(250 mm×4.6 mm,3 μm) was adopted, the mobile phase consisted of acetonitrile-0.04 mol·L-1 ammonium acetate aqueous solution with gradient elution. The flow rate was 1.0 mL·min-1, the column temperature was 25 ℃, the detection wavelength was 249 nm and the injection volume was 10 μL. Results: The chromatographic peaks of ixabepilone and its seven related substances were well separated. A good linear relationship was shown between the mass concentration of 1-7 related substances of ixabepilone and the corresponding peak area within the concentration range of 0.05-2 μg·mL-1(r≥0.999 5). The limits of quantification were 0.025, 0.033, 0.043, 0.036, 0.036, 0.108 and 0.032 μg·mL-1, respectively, and the average recoveries (n=9) were 98.5%, 98.3%, 101.2%, 100.3%, 97.6%, 101.0% and 98.6% with RSDs of 2.3%, 2.8%, 3.3%, 2.1%, 2.6%, 5.7% and 3.6%, respectively. The detection results of 3 batches of ixabepilone samples showed that the contents of known impurities and other maximum single impuritie were less than 0.083%, and the total content of impurities was less than 0.256%. Conclusion: The detection method has demonstrated strong specificity and high accuracy, it could be used for the related substances of ixabepilone API, and fill the blank of the detection method of related substances of ixabepilone at home and abroad.

参考文献

[1] CAO DS, JIANG SL, GUAN YD, et al. A multi-scale systems pharmacology approach uncovers the anti-cancer molecular mechanism of ixabepilone[J].Eur J Med Chem, 2020, 199: 112421
[2] GALANIS E, ANDERSON SK, TWOHY EL, et al. A phase 1 and randomized, placebo-controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872[J].Cancer, 2019, 125(21):3790
[3] RASHEED W, FLAIM B, SEYMOUR JF, et al. Reversible severe pulmonary hypertension secondary to dasatinib in a patient with chronic myeloid leukemia[J].Leuk Res, 2009, 33(6):861
[4] MORISHITA S, HAGIHARA M, ITABASHI M, et al. Development of pulmonary arterial hypertension during oral dasatinib therapy for chronic myelogenous leukemia[J].Rinsho Ketsueki, 2016, 57(8):999
[5] 徐家根, 赵春才, 吴学平, 等. HPLC法测定达沙替尼片中主药和有关物质的含量[J].中国药房, 2011, 22(1):56
XU JG, ZHAO CC, WU XP, et al. Determination of main drug and related substances in dasatinib tablets by HPLC[J].China Pharm, 2011, 22(1):56
[6] MESTERMANN K, GIAVRIDIS T, WEBER J, et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells[J].Sci Transl Med, 2019, 11(499):eaau5907
[7] NAKAMAE H, FUJISAWA S, OGURA M, et al. Dasatinib versus imatinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia: a subanalysis of the DASISION 5-year final report[J].Int J Hematol, 2017, 105(6):792
[8] SHAH NP, ROUSSELOT P, SCHIFFER C, et al. Dasatinib in imatinib-resistant or intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034[J].Am J Hematol, 2016, 91(9):869
[9] 黄玉, 吕华, 陈建秋, 等. HPLC法测定达沙替尼含量及有关物质[J].海峡药学, 2013, 25(7):72
HUANG Y, LÜ H, CHEN JQ, et al. Determination of dasatinib and its related substances by HPLC[J].Strait Pharm J, 2013, 25(7):72
[10] 李玥婷, 施鹏旭, 英子伟. 曲妥珠单抗联合伊沙匹隆对晚期转移性乳腺癌患者的疗效及CEA、CA125、CA15-3水平的影响[J].中国医学创新, 2018, 15(23):63
LI YT, SHI PX, YING ZW. Effect of trastuzumab combined with isapirone on the level of CEA, CA125 and CA15-3 in patients with advanced metastatic breast cancer[J].Med Innov China, 2018,15(23):63
[11] 黄任平. 曲妥珠单抗联合伊沙匹隆治疗晚期转移性乳腺癌的疗效观察[J].河北医学, 2017, 23(10):1598
HUANG RP. Trastuzumab combined with isapirone in the treatment of advanced metastatic breast cancer[J].Hebei Med Sci, 2017,23 (10):1598
[12] 李惠莹. 抗乳腺癌新药―伊沙匹隆的药理与临床应用[J].中国热带医学, 2010, 10(5):621
LI HY. Pharmacological and clinical application of new drug for breast cancer-isapirone[J].Chin J Trop Med, 2010, 10(5):621
[13] 赵娜, 严拯宇, 姜新民. 达沙替尼及其有关物质的HPLC法测定[J].中国医药工业杂志, 2012, 43(2):129
ZHAO N, YAN ZY, JIANG XM. Determination of dasatinib and its related substances by HPLC[J].Chin J Pharm, 2012, 43 (2):129
[14] 郝春芳, 佟仲生. 伊沙匹隆治疗转移性乳腺癌的临床研究进展[J].中华乳腺病杂志(电子版), 2010, 4(6):661
HAO CF, TONG ZS. Clinical research progress of isapirone in the treatment of metastatic breast cancer[J].Chin J Breast Dis(Electron Ed), 2010, 4(6):661
[15] 胡跃民, 白秋江, 赵军, 等. 治疗乳腺癌新药—伊沙匹隆[J].医药导报, 2009, 28(10):1362
HU YM, BAI QJ, ZHAO J, et al. A new drug for the treatment of breast cancer ixabepilone [J].Her Med, 2009, 28(10):1362
[16] 马素柯. 伊沙匹隆联合水飞蓟宾对人卵巢癌SKOV3细胞株血管生成作用的影响[D].长春:吉林大学, 2016
MA SK. Effect of Ixabepilone Combined with Silibinin on Angiogenesis of Human Ovarian Cancer SKOV3 Cell Line[D].Changchun: Jilin University, 2016
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