HPLC-加校正因子的主成分自身对照法同时测定琥珀酸索利那新原料药中7种有关物质
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摘要
目的:建立同时测定琥珀酸索利那新原料药中7种有关物质的方法。方法:采用HPLC法。色谱柱为Thermo Hypersil ODS C18,流动相为0.02 mol/L KH2PO4(含0.2%三乙胺,pH 3.0)-乙腈溶液(梯度洗脱),流速为1.2 mL/min,检测波长为210 nm,柱温为40℃,进样量为20μL;绘制琥珀酸索利那新和杂质A、C、D、I、J、K、L的回归方程,以斜率计算各杂质相对于琥珀酸索利那新的校正因子,并测定3批琥珀酸索利那新原料药中杂质A、C、D、I、J、K、L的含量。结果:杂质A、C、D、I、J、K、L的检测质量浓度线性范围分别为0.148 1~0.740 3、0.142 9~0.714 5、0.141 1~0.705 6、0.148 9~0.744 6、0.152 0~0.759 9、0.137 9~0.689 6、0.020 0~0.100 0μg/mL(r=0.999 8或0.999 9或1.000 0),校正因子分别为0.51、0.40、0.41、0.91、0.47、0.85、1.23,检测限分别为0.049 3、0.047 6、0.047 0、0.048 1、0.050 7、0.046 0、0.006 7μg/m L,定量限分别为0.148 1、0.142 9、0.141 1、0.148 9、0.152 0、0.137 9、0.020 0μg/m L,精密度、稳定性(24 h)、重复性试验的RSD均<5.0%(n=6),平均回收率分别为101.09%、97.58%、93.77%、98.56%、99.68%、97.07%、93.54%,RSD分别为0.75%、0.51%、0.47%、0.84%、0.70%、0.75%、1.21%(n=9)。3批琥珀酸索利那新原料药中杂质I含量为0.015%~0.018%,其余杂质未检出。结论:该方法灵敏度高、准确可靠,可用于琥珀酸索利那新原料药中有关物质的测定。
OBJECTIVE:To establish method for simultaneous determination of 7 related substances in solifenacin succinate raw material. METHODS:HPLC method was adopted. The determination was performed on Thermo Hypersil ODS C18 column with mobile phase consisted of 0.02 mol/L KH2 PO4(0.02% triethylamine,pH=3.0)-acetonitrile(gradient elution)at the flow rate of 1.2 mL/min. The detection wavelength was set at 210 nm,and column temperature was 40 ℃. The sample size was 20 μL. The regression equation of solifenacin succinate and impurity A,C,D,I,J,K,L were drawn. Correction factors of impurities to solifenacin succinate were calculated with slope. The contents of impurities A,C,D,I,J,K and L were determined in 3 batchesof solifenacin succinate raw material. RESULTS:The linear ranges of impurity A,C,D,I,J,K and L were 0.148 1-0.740 3,0.142 9-0.714 5,0.141 1-0.705 6,0.148 9-0.744 6,0.152 0-0.759 9,0.137 9-0.689 6,0.020 0-0.100 0 μg/m L(r=0.999 8,0.999 9 or 1.000 0),respectively. The relative correction factors were 0.51,0.40,0.41,0.91,0.47,0.85,1.23. The limits of detection were 0.049 3,0.047 6,0.047 0,0.048 1,0.050 7,0.046 0,0.006 7 μg/mL. The quantification limits were 0.148 1,0.142 9,0.141 1,0.148 9,0.152 0,0.137 9,0.020 0 μg/mL,respectively. RSDs of precision,stability(24 h)and reproducibility tests were all lower than 5.0%(n=6). Average recoveries were 101.09%,97.58%,93.77%,98.56%,99.68%,97.07% and 93.54%;RSDs were 0.75%,0.51%,0.47%,0.84%,0.70%,0.75%,1.21%(n=9). The contents of impurity I in 3 batches of solifenacin succinate raw material were 0.015%-0.018%,other impurities were not detected. CONCLUSIONS:The method is sensitive,accurate and reliable,which can be used to determine the related substances of solifenacin succinate raw material.
OBJECTIVE:To establish method for simultaneous determination of 7 related substances in solifenacin succinate raw material. METHODS:HPLC method was adopted. The determination was performed on Thermo Hypersil ODS C18 column with mobile phase consisted of 0.02 mol/L KH2 PO4(0.02% triethylamine,pH=3.0)-acetonitrile(gradient elution)at the flow rate of 1.2 mL/min. The detection wavelength was set at 210 nm,and column temperature was 40 ℃. The sample size was 20 μL. The regression equation of solifenacin succinate and impurity A,C,D,I,J,K,L were drawn. Correction factors of impurities to solifenacin succinate were calculated with slope. The contents of impurities A,C,D,I,J,K and L were determined in 3 batchesof solifenacin succinate raw material. RESULTS:The linear ranges of impurity A,C,D,I,J,K and L were 0.148 1-0.740 3,0.142 9-0.714 5,0.141 1-0.705 6,0.148 9-0.744 6,0.152 0-0.759 9,0.137 9-0.689 6,0.020 0-0.100 0 μg/m L(r=0.999 8,0.999 9 or 1.000 0),respectively. The relative correction factors were 0.51,0.40,0.41,0.91,0.47,0.85,1.23. The limits of detection were 0.049 3,0.047 6,0.047 0,0.048 1,0.050 7,0.046 0,0.006 7 μg/mL. The quantification limits were 0.148 1,0.142 9,0.141 1,0.148 9,0.152 0,0.137 9,0.020 0 μg/mL,respectively. RSDs of precision,stability(24 h)and reproducibility tests were all lower than 5.0%(n=6). Average recoveries were 101.09%,97.58%,93.77%,98.56%,99.68%,97.07% and 93.54%;RSDs were 0.75%,0.51%,0.47%,0.84%,0.70%,0.75%,1.21%(n=9). The contents of impurity I in 3 batches of solifenacin succinate raw material were 0.015%-0.018%,other impurities were not detected. CONCLUSIONS:The method is sensitive,accurate and reliable,which can be used to determine the related substances of solifenacin succinate raw material.
引文
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[2]金柯,王志荣,宣枫,等.联用琥珀酸索利那新片和坦索罗辛缓释胶囊治疗女性膀胱过度活动症的效果评析[J].当代医药论丛,2018,16(5):177-178.
[3]马江,李小顺,董维平,等.琥珀酸索利那新片治疗膀胱过度活动症的效果分析[J].现代生物医学进展,2016,16(31):6100-6102.
[4]张唯力,胡自力,胡蓉,等.国产酒石酸托特罗定片治疗膀胱过度活动症的临床研究[J].中国药房,2001,12(2):40-41.
[5]袁道彰,徐晓龙,黄兰珍,等.索利那新治疗膀胱过度活动症疗效观察[J].中国现代医学杂志,2014,24(6):101-103.
[6]LIU M,WANG JY,YANG Y,et al.Overactive bladder symptom score to evaluate efficacy of solinacin for the treatment of overactive bladder symptoms[J].Chin Med J,2014,127(2):261-265.
[7]那彦群,叶章群,孙颖浩,等.中国泌尿外科疾病诊断治疗指南:膀胱过度活动症诊治指南[S].北京:人民卫生出版社,2013:330-333.
[8]APOSTOLIDIS A.Antimuscarinics in the treatment of OAB:is there a first-line and a second-line choice?[J].Current Drug Targets,2015,16(11):1187-1197.
[9]WANG Y,XU K,HU H,et al.Prevalence,risk factors,and impact on health related quality of life of overactive bladder in China[J].Neurourol Urodyn,2011,30(8):1448-1455.
[10]European Pharmacopoeia Commission.European Pharmacopoeia:9.3[S].S.I.:European Directorate for the Quality of Medicines,2016:4991-4992.
[11]The United States Pharmacopieial Convention.U.S.Pharmacopoeia[EB/OL].[2018-06-01].http://zy.yaozh.com/foreign/USPPharmArchives/41(5)%20InProcess%20Revision%20Solifenacin%20Succinate.pdf.
[12]李艳贞,王成港.HPLC法测定琥珀酸索利那新原料中有关物质[J].现代药物与临床,2018,33(7):1573-1578.
[13]喻颜,赵劲松,张弘.HPLC测定琥珀酸索利那新片中的有关物质[J].华西药学杂志,2017,32(2):214-216.
[14]龚俊强.琥珀酸索利那新片的制剂工艺及质量研究[D].杭州:浙江大学,2015.
[15]International Council for Harmonization.Harmonised tripatite guideline.Impurities in new drug substances Q3A(R2)(2006)[EB/OL].[2018-06-09].https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3A_R2/Step4/Q3A_R2_Guideline.pdf.