基于对照制剂的沉香化气丸多组分含量测定研究

目的：建立沉香化气丸的多组分含量测定方法；研制沉香化气丸对照制剂，随行测定，并将其用于质量评价。方法：采用GC法测定乙酸龙脑酯、百秋李醇、吉马酮、去氢木香内酯4个成分的含量，使用DB-17毛细管柱（30 m×0.25 mm，膜厚度为0.25 μm），程序升温，进样口温度为200℃，检测器（FID）温度为250℃，分流比为5∶1；采用HPLC法测定沉香四醇的含量，使用Phenomenex Luna C₁₈色谱柱（4.6 mm×250 mm，5 μm），以乙腈（A）-0.1%甲酸溶液（B）为流动相，梯度洗脱，检测波长252 nm，流速1 mL·min^-1，柱温40℃，进样量20 μL；采用UPLC波长切换法同时测定甘草苷、芸香柚皮苷、橙皮苷、甘草酸、木香烃内酯和广藿香酮6个成分的含量，使用Phenomenex Kinetex C₁₈色谱柱（4.6 mm×100 mm，2.7 μm），以乙腈（A）-0.1%磷酸水溶液（B）为流动相，梯度洗脱，分段变波长测定，流速0.8 mL·min^-1，柱温35℃，进样量2 μL。研制沉香化气丸对照制剂，随行测定，并将其用于质量评价。结果：对照制剂中的沉香四醇、百秋李醇、甘草苷、芸香柚皮苷、橙皮苷、甘草酸、去氢木香内酯和木香烃内酯的总量、广藿香酮含量分别为0.150、0.39、0.33、0.82、5.53、0.88、1.17、0.20 mg·g^-1；37批样品中百秋李醇、甘草苷、芸香柚皮苷、橙皮苷、甘草酸、去氢木香内酯和木香烃内酯的总量、广藿香酮的含量测定结果分别为0.02~0.20、0.18~0.75、0.49~3.03、4.13~12.26、0.38~0.86、0.28~2.75、0.13~0.33 mg·g^-1，4家生产企业的37批样品均有组分未能达到拟定的含量限度（百秋李醇、沉香四醇、甘草苷、橙皮苷、甘草酸、去氢木香内酯和木香烃内酯的总量、广藿香酮、芸香柚皮苷的含量限度分别为0.11、0.030、0.21、1.67、0.67、0.53、0.10、0.41 mg·g^-1），22批样品未检出沉香四醇。结论：所建方法准确、简便、客观，可更加全面地控制沉香化气丸的质量。

Objective: To establish a multi-component determination method for Chenxiang Huaqi pills.Chenxiang Huaqi pills reference drug was developed and used for quality evaluation.Methods: GC method for the determination of bonyl acetate,patchouli alcohol,germacrone and dehydrocostus lactone in Chenxiang Huaqi pills was performed on a DB-17 capillary column (30 m×0.25 mm,0.25 μm)with temperature programming.Temperature of the inlet and the detector were 200℃ and 250℃,respectively.The split ratio was 5:1.HPLC method for the determination of agarotetrol was performed on a Phenomenez Luna C₁₈ column (4.6 mm×250 mm,5 μm),with gradient elution of acetonitrile (A)-0.1% formic acid.The detection wavelength was 252 nm,the flow rate was 1 mL·min^-1,the column temperature was 40℃,and the injection volume was 20 μL.UPLC with wavelength switching method for the determination of liquiritin,narirutin,hesperidin,glycyrrhizicacid,costunolide and pogostone in Chenxiang Huaqi pills was performed on a Phenomenex Kinetex C₁₈ column (4.6 mm×250 mm, 5 μm)with gradient elution of acetonitrile and 0.1% phosphoric acid at a flow rate of 0.8 mL·min^-1.The column temperature was 40℃ and the injection volume was 20 μL.Results: Contents of agarotetrol,patchouli alcohol,liquiritin,narirutin,hesperidin,glycyrrhizic acid,total content of dehydrocostus lactone and costunolide,and pogostone in reference drug were 0.150,0.39,0.33,0.82,5.53,0.88,1.17 and 0.20 mg·g^-1,respectively.The contents in 37 samples were in the ranges of 0.02-0.20 mg·g^-1 for patchouli alcohol,0.18-0.75 mg·g^-1 for liquiritin,0.49-3.03 mg·g^-1 for narirutin,4.13-12.26 mg·g^-1 for hesperidin,0.38-0.86 mg·g^-1 for glycyrrhizic acid,0.28-2.75 mg·g^-1 for dehydrocostus lactone and costunolide and 0.13-0.33 mg·g^-1 for pogostone,respectively.37 samples from four manufacturers failed to reach the proposed limits (the proposed limits for patchoulialcohol,agarotetrol,liquiritin,hesperidin,glycyrrhizic acid,total content of dehydrocostus lactone and costunolide,pogostone and narirutin were 0.11,0.030,0.21,1.67,0.67,0.53,0.10 and 0.41 mg·g^-1,respectively),and agarotetrol was not detected in 22 samples.Conclusion: The proposed methods are accurate,simple and objective,which offer a more comprehensive approach for quality control of Chenxiang Huaqi pills.

[1] 中华人民共和国药典2015年版.一部[S].2015:990 ChP 2015.Vol Ⅰ[S].2015:990
[2] 潘玄玄,宋粉云,李华,等.UPLC波长切换法同时测定沉香化气丸中7个成分的含量[J].药物分析杂志,2017,37(10):1832 PAN XX,SONG FY,LI H,et al.Simultaneous determination of seven components in Chenxiang Huaqi pills by UPLC with wavelength switching[J].Chin J Pharm Anal,2017,37(10):1832
[3] 马丽娜,郭伟英.毛细管气相色谱法同时测定沉香化气丸中3个成分的含量[J].药物分析杂志,2012,32(9):1559 MA LN,GUO WY.Simultaneous determination of three components in Chenxiang Huaqi pills by capillary GC[J].Chin J Pharm Anal,2012,32(9):1559
[4] 郭琪,闫艳,王海波,等.HPLC波长切换法同时测定清热解毒颗粒中8个成分的含量[J].药物分析杂志,2015,35(9):1601 GUO Q,YAN Y,WANG HB,et al.Determination of eightcomponents in Qingrejiedu granules by HPLC with UV switch[J].Chin J Pharm Anal,2015,35(9):1601
[5] 张小龙,孙晓,姚晨旭,等.GC法同时测定肚痛丸中6种有效成分的含量[J].中国药师,2018,21(3):518 ZHANG XL,SUN X,YAO CX,et al.Simultaneous determination of six effective components in Dutong pills by GC[J].China Pharm,2018,21(3):518
[6] 尤立华,杨秉呼,叶萌,等.气相色谱法同时测定大活络胶囊多组分含量[J].中国药业,2014,23(19):38 YOU LH,YANG BH,YE M,et al.Simultaneous determination of various components in Dahuoluo capsule by GC[J].China Pharm,2014,23(19):38
[7] 田志杰.气相色谱法同时测定复方樟脑乳膏中4种成分含量[J].中国药品标准,2018,19(2):141 TIAN ZJ.Simultaneous determination of four constituents in compound camphor cream by GC[J].Drug Stand China,2018,19(2):141
[8] 孙云鹏,汪琛媛,王国凯,等.四味黄连洗剂的UPLC指纹图谱研究及主成分的含量测定[J].华西药学杂志,2017,32(6):629 SUN YP,WANG CY,WANG GK,et al.Study on the UPLC fingerprint and determination of index components of Siwei Huanglian lotion[J].West China J Pharm Sci,2017,32(6):629
[9] 王丹丹,闫艳,张福生,等.远志药材UPLC指纹图谱及多指标性成分测定方法的建立[J].中草药,2018,49(5):1150 WANG DD,YAN Y,ZHANG FS,et al.Establishment for methods of fingerprint analysis and determination of index compounds on commercial Polygala tenuifolia by ultra performance liquid chromatography[J].Chin Tradit Herb Drugs,2018,49(5):1150
[10] 聂黎行,戴忠,马双成.中药对照制剂研制指导原则和技术要求[J].中国中药杂志,2017,42(9):1601 NIE LX,DAI Z,MA SC.Guideline principle and technical requirement for preparing traditional Chinese medicine reference drug[J].Chin J Tradit Chin Med,2017,42(9):1601
[11] 孙国祥,张宇,高嘉悦,等.内标定量指纹图谱法筛选冠心苏合丸对照制剂[J].中草药,2014,45(5):642 SUN GX,ZHANG Y,GAO JY,et al.Selection of Guanxin Suhe pill reference preparation by internal standard quantified fingerprints method[J].Chin Tradit Herb Drugs,2014,45(5):642
[12] 聂黎行,查祎凡,胡晓茹,等.基于对照制剂的牛黄清胃丸全处方鉴别研究和等级初评价[J].中草药,2018,49(22):5320 NIE LX,ZHA YF,HU XR,et al.Whole-ingredient identification and primary grade evaluation of Niuhuang Qingwei pills based on reference drug[J].Chin Tradit Herb Drugs,2018,49(22):5320
[13] 杨立伟,王海南,耿莲,等.基于标准汤剂的中药整体质量控制模式探讨[J].中国实验方剂学杂志,2018,24(8):1 YANG LW,WANG HN,GENG L,et al.Discussion on whole quality control mode of traditional Chinese medicine based on standard decoction[J].Chin J Exp Tradit Med Form,2018, 24(8):1