目的: 建立HPLC法同时测定氯雷他定原料药中9个有关物质(杂质A～I)。方法: 采用YMC-Triart C18(250 mm×4.6 mm,5 μm)色谱柱,以庚烷磺酸钠缓冲液-乙腈为流动相,梯度洗脱,流速1.0 mL·min-1,柱温40 ℃,检测波长254 nm,进样体积20 μL。结果: 对照品氯雷他定与9个已知杂质A~I的色谱峰均能良好分离,对照品氯雷他定及杂质A~I分别在0.215～10.712 μg·mL-1(r=0.999 9)、0.544～10.930 μg·mL-1(r=0.999 9)、0.202～10.108 μg·mL-1(r=1.000)、0.202～10.141 μg·mL-1(r=1.000)、0.198～9.923 μg·mL-1(r=1.000)、0.580～11.625 μg·mL-1(r=1.000)、0.489～9.783 μg·mL-1(r=0.999 9)、0.223～11.249 μg·mL-1(r=1.000)、0.197～9.874 μg·mL-1(r=0.999 9)、0.199～9.971 μg·mL-1(r=1.000)浓度范围内线性关系良好(n=6);对照品氯雷他定及杂质A~I的定量限分别为0.078、0.302、0.146、0.102、0.075、0.251、0.242、0.088、0.196、0.127 μg·mL-1;杂质A~I的平均回收率(n=9)分别为98.1%、100.0%、97.4%、100.2%、98.3%、102.1%、102.0%、100.0%、97.3%;4个厂家氯雷他定原料药测定结果显示,1个厂家的样品中杂质F的含量较高,应引起重视。结论: 该方法灵敏度高,专属性强,可区分不同厂家氯雷他定原料药的质量,可用于氯雷他定原料药的有关物质检查。
Objective: To establish an HPLC method for simultaneous determination of 9 related substances including impurity A-I in loratadine. Methods: The determination was performed on a YMC-Triart C18 column(250 mm×4.6 mm,5 μm). The mobile phase consisted of sodium heptanesulfonate buffer solution and acetonitrile with gradient elution. The flow rate was 1.0 mL·min-1, the column temperature was maintained at 40 ℃, the detection wavelength was set at 254 nm, and the injection volume was 20 μL. Results: The resolutions between the peaks of reference substance loratadine and nine known impurities (including impurities A-I) were good. The calibration curves of reference substance loratadine and impurities A-I were linear in their respective weight ranges of 0.215-10.712 μg·mL-1(r=0.999 9), 0.544-10.930 μg·mL-1(r=0.999 9), 0.202-10.108 μg·mL-1(r=1.000), 0.202-10.141 μg·mL-1(r=1.000), 0.198-9.923 μg·mL-1(r=1.000), 0.580-11.625 μg·mL-1(r=1.000 0), 0.489-9.783 μg·mL-1(r=0.999 9), 0.223-11.249 μg·mL-1(r=1.000), 0.197-9.874 μg·mL-1(r=0.999 9)and 0.199-9.971 μg·mL-1(r=1.000). The limits of quantitation were 0.078, 0.302, 0.146, 0.102, 0.075, 0.251, 0.242, 0.088, 0.196 and 0.127 μg·mL-1. The recoveries (n=9) of impurities A-I were 98.1%, 100.0%, 97.4%, 100.2%, 98.3%, 102.1%, 102.0%, 100.0% and 97.3%, respectively. The determination results of the four manufactures samples showed that the content of impurity F of one manufacture was high, which worthed attention. Conclusion: This method is sensitive and specific, which can distinguish the quality of loratadine from different manufacturers, and can be used for the determination of related substances in loratadine API.
[1] 马坚池,卢秀仪,唐增奇. 氯雷他定治疗慢性荨麻疹的有效性分析与评定[J].现代诊断与治疗, 2017, 28(14):2567
MA JC, LU XY, TANG ZQ. Analysis and evaluation of the effectiveness of loratadine in the treatment of chronic urticaria[J].Mod Diagn Treat, 2017, 28(14):2567
[2] 田歌,钟舒阳,彭崇信,等. 氯雷他定联合双氯芬酸钠滴眼液治疗过敏性结膜炎的临床价值[J].国际眼科杂志, 2021, 21(3):421
TIAN G, ZHONG SY, PENG CX, et al. Clinical value of loratadine combined with diclofenac sodium eye drops in the treatment of allergic conjunctivitis[J].Int Eye Sci, 2021, 21(3):421
[3] 刘春阳. 氯雷他定联合西咪替丁治疗小儿过敏性紫癜的效果观察[J].当代医学, 2021, 27(17):174
LIU CY. Effect of loratadine combined with cimetidine on henoch shonlein purpura in children[J].Contemp Med, 2021, 27(17):174
[4] 杜云. 氯雷他定治疗过敏性皮炎的临床效果观察[J].中国卫生标准管理,2021, 12(20):64
DU Y. Clinical effect of loratadine on allergic dermatitis[J].China Health Stand Manag, 2021, 12(20):64
[5] 李剑雄, 胡新军. 孟鲁司特钠联合氯雷他定治疗哮喘患儿的效果及对血清炎性因子水平的影响[J].中国医学创新, 2021, 18(25):86
LI JX, HU XJ. Effect of montelukast sodium combined with loratadine in the treatment of asthmatic children and its effect on the level of serum inflammatory factors[J].Med Innovat China, 2021, 18(25):86
[6] 付静寨,王玉清,及艳辉,等. 氯雷他定对降低冠状动脉粥样硬化血管造影中过敏反应的临床研究[J].河北医药, 2018, 40(19):2946
FU JZ, WANG YQ, JI YH, et al. The effect of loratadine on the related indexes in coronary atherosclerotic angiography[J].Hebei Med J, 2018, 40(19):2946
[7] 夏学励. 氯雷他定片的制备及质量控制[J].中国药房, 2006, 17(21):1624
XIA XL. Preparation and quality control of loratadine tablets[J].China Pharm, 2006, 17(21):1624
[8] 王玉,郑淑凤,郭伟斌,等. 氯雷他定片质量评价研究[J].药物评价研究, 2018, 41(7):1256
WANG Y, ZHENG SF, GUO WB, et al. Analysis and evaluation of loratadine tablets[J].Drug Eval Res, 2018, 41(7):1256
[9] 康军,张鹤. HPLC法测定氯雷他定片含量[J].中国医药导报, 2021, 8(4):56
KANG J, ZHANG H. Content determination of loratadine tablets by HPLC[J].China Med Herald, 2021, 8(4):56
[10] 崔京, 黄健, 霍立茹, 等. 氯雷他定片含量及有关物质的HPLC测定[J].中国医药工业杂志, 2002, 33(6):294
CUI J, HUANG J, HUO LR, et al. Determination of loratadine tablets and its related substances by HPLC[J].Chin J Pharm, 2002, 33(6):294
[11] 唐立超, 郭伟斌, 郑淑凤, 等. HPLC测定氯雷他定的含量及其有关物质[J].中国现代应用药学, 2014, 31(8):994
TANG LC, GUO WB, ZHENG SF, et al. Determination of content and related substances of loratadine by HPLC[J].Chin J Mod Appl Pharm, 2014, 31(8):994
[12] 马超, 周颖, 童元峰, 等. HPLC/DAD/MS法测定氯雷他定及其微量杂质[J].药物分析杂志, 2010, 30(11):2007
MA C, ZHOU Y, TONG YF, et al. HPLC/DAD/MS determination of loratadine and its impurities[J].Chin J Pharm Anal, 2010, 30(11):2007
[13] 中华人民共和国药典2020年版. 二部[S].2020:1657
ChP 2020. Vol Ⅱ[S].2020:1657
[14] USP 43-NF 38[S].2021:2672
[15] EP 10.0[S].2021:3337
