Article(id=1240709664451654197, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1240709662501294254, articleNumber=null, orderNo=null, doi=10.16155/j.0254-1793.2024-0395, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1718294400000, receivedDateStr=2024-06-14, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773737835276, onlineDateStr=2026-03-17, pubDate=1743350400000, pubDateStr=2025-03-31, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773737835276, onlineIssueDateStr=2026-03-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773737835276, creator=13701087609, updateTime=1773737835276, updator=13701087609, issue=Issue{id=1240709662501294254, tenantId=1146029695717560320, journalId=1205117023404326918, year='2025', volume='45', issue='3', pageStart='361', pageEnd='542', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1773737834810, creator=13701087609, updateTime=1773737909503, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240709975845163177, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1240709662501294254, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240709975845163178, tenantId=1146029695717560320, journalId=1205117023404326918, issueId=1240709662501294254, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=400, endPage=408, ext={EN=ArticleExt(id=1240709664703312443, articleId=1240709664451654197, tenantId=1146029695717560320, journalId=1205117023404326918, language=EN, title=Simultaneou determination of 22 components in Bimin capsules by UPLC-MS/MS*, columnId=1206272756333736276, journalTitle=Chinese Journal of Pharmaceutical Analysis, columnName=Ingredient Analysis, runingTitle=null, highlight=null, articleAbstract=

Objective: To establish an ultra-high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for the simultaneous determination of 22 components of Bimin capsules, including benzoylaconine, benzoylmesaconine, benzoylhypacoitine, hypaconitine, mesaconitine, fuziline, aconitine, aconine,mesaconine, isoliquiritigenin, echinatin, protocatechuic acid, liquiritigenin, isoliquiritoside, glycycoumarin,naringenin, schaftoside, licochalcone B, glycyrrhizic acid ammonium salt, liquiritin, liquiritin apioside and isoliquiritin apioside. Methods: The AcclaimTM RSLC 120C18 column (2.1 mm×100 mm, 2.2 μm) was used with 0.05% formic acid water (A) and acetonitrile (B) as the mobile phase at a flow rate of 0.4 mL · min-1. Electrospray ionization (ESI) source and multiple reaction monitoring (MRM) mode in both positive and negative were used for ion detections. Resulets:The 22 components displayed a good linear relationship (R2>0.990) in their respective ranges, and the precision, repeatability, stability, and sample recovery rate all met the requirements. It was found that all 22 components were detected in the nasal sensitivity capsules, with significant differences in the content of some components. Conclusion: This method is fast, simple, sensitive and reliable, and can provide scientific basis for the quality control of the Bimin capsules.

, correspAuthors=Yu-qing WANG, Shan-xin LIU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Lei CAO, Jian-yun BI, Yu-qing WANG, Xin-jun ZHANG, Ming SU, Bo-yang WANG, Xin-rui LI, Xin-ru SUN, Kang-ning XIAO, Yu-jie HOU, Sheng-mei LIU, Qian ZHOU, Shan-xin LIU), CN=ArticleExt(id=1240709665349235277, articleId=1240709664451654197, tenantId=1146029695717560320, journalId=1205117023404326918, language=CN, title=UPLC-MS/MS法同时测定鼻敏胶囊中22个成分的含量*, columnId=1206272756476342615, journalTitle=药物分析杂志, columnName=成分分析, runingTitle=null, highlight=null, articleAbstract=

目的:建立超高效液相色谱串联质谱(UPLC-MS/MS)方法同时测定鼻敏胶囊样品中苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱、次乌头碱、新乌头碱、附子灵、乌头碱、乌头原碱、新乌头原碱、异甘草素、刺甘草查尔酮、原儿茶酸、甘草素、异甘草苷、甘草香豆素、柚皮素、夏佛塔苷、甘草查尔酮B、甘草酸铵、甘草苷、芹糖甘草苷、芹糖异甘草苷22个成分的含量。方法:采用AcclaimTM RSLC 120C18型色谱柱(2.1 mm×100 mm,2.2 μm),以0.05%甲酸水(A)-乙腈(B)为流动相,梯度洗脱,流速为0.4 mL · min-1;采用电喷雾离子源(ESI)、多反应检测(MRM)模式进行正、负离子检测。结果:22个成分在各自的范围内线性关系良好(R2>0.990),精密度、重复性、稳定性、加样回收率等均符合要求。结果发现,22个成分在鼻敏胶囊中均被检测到,个别成分含量相差较大。结论:该方法快速、简便、灵敏、可靠,可为鼻敏胶囊的质量控制提供科学依据。

, correspAuthors=王玉清, 刘善新, authorNote=null, correspAuthorsNote=
**王玉清 Tel:(0531)82949813;E-mail:;
刘善新 Tel:(0531)82949813;E-mail:
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unstructuredReference=陈会朋,王银,余惠旻,.基于UPLC-Q-TOF/MS技术分析加味左金丸化学成分及指纹图谱研究[J].中草药202354(14):4442, articleTitle=基于UPLC-Q-TOF/MS技术分析加味左金丸化学成分及指纹图谱研究, refAbstract=null), Reference(id=1243919072514126335, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2023, volume=54, issue=14, pageStart=4442, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=32, authorNames=CHEN HP, WANG Y, YU HW, journalName=Chin Tradit Herb Drugs, refType=null, unstructuredReference=CHEN HPWANG YYU HWet al.Chemical components and chromatographic fingerprints of Jiawei Zuojin pill based on UPLC-Q-TOF/MS[J].Chin Tradit Herb Drugs202354(14):4442, articleTitle=Chemical components and chromatographic fingerprints of Jiawei Zuojin pill based on UPLC-Q-TOF/MS, refAbstract=null), Reference(id=1243919072589623808, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2024, volume=30, issue=6, pageStart=169, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=33, authorNames=姜奇瑶, 刘臣臣, 陈惠玲, journalName=中国实验方剂学杂志, refType=null, unstructuredReference=姜奇瑶,刘臣臣,陈惠玲,.基于UPLC-Q-TOF-MS/MS和UPLC的六君子汤化学成分定性与定量分析[J].中国实验方剂学杂志202430(6):169, articleTitle=基于UPLC-Q-TOF-MS/MS和UPLC的六君子汤化学成分定性与定量分析, refAbstract=null), Reference(id=1243919072744813057, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2024, volume=30, issue=6, pageStart=169, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=34, authorNames=JIANG QY, LIU CC, CHEN HL, journalName=Chin J Exp Tradit Med Form, refType=null, unstructuredReference=JIANG QYLIU CCCHEN HLet al.Qualitative and quantitative analysis of chemical constituents in Liu Junzitang by UPLC-Q-TOF-MS/MS and UPLC[J].Chin J Exp Tradit Med Form202430(6):169, articleTitle=Qualitative and quantitative analysis of chemical constituents in Liu Junzitang by UPLC-Q-TOF-MS/MS and UPLC, refAbstract=null), Reference(id=1243919072820310530, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2022, volume=44, issue=4, pageStart=1198, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=35, authorNames=代珊, 朱红梅, 李帅, journalName=中成药, refType=null, unstructuredReference=代珊,朱红梅,李帅,.UPLC-MS/MS法测定不同附子炮制品中14种生物碱[J].中成药202244(4):1198, articleTitle=UPLC-MS/MS法测定不同附子炮制品中14种生物碱, refAbstract=null), Reference(id=1243919072904196611, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2022, volume=44, issue=4, pageStart=1198, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=36, authorNames=DAI S, ZHU HM, LI S, journalName=Chin Tradit Pat Med, refType=null, unstructuredReference=DAI SZHU HMLI Set al.Determination of fourteen alkaloids in different processed products of Aconiti Lateralis Radix Praeparata by UPLC-MS/MS[J].Chin Tradit Pat Med202244(4):1198, articleTitle=Determination of fourteen alkaloids in different processed products of Aconiti Lateralis Radix Praeparata by UPLC-MS/MS, refAbstract=null), Reference(id=1243919073017442820, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2022, volume=45, issue=1, pageStart=1448, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=37, authorNames=田萍, 马开, 张薇, journalName=中药材, refType=null, unstructuredReference=田萍,马开,张薇,.UPLC-MS/MS同时测定真武汤中16个成分的含量[J].中药材202245(1):1448, articleTitle=UPLC-MS/MS同时测定真武汤中16个成分的含量, refAbstract=null), Reference(id=1243919073084551685, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2022, volume=45, issue=1, pageStart=1448, pageEnd=null, url=null, language=null, rfNumber=[22], rfOrder=38, authorNames=TIAN P, MA K, ZHANG W, journalName=J Chin Med Mater, refType=null, unstructuredReference=TIAN PMA KZHANG Wet al.UPLC-MS/MS simultaneously determined the content of 16 components in Zhenwu decoction[J].J Chin Med Mater202245(1):1448, articleTitle=UPLC-MS/MS simultaneously determined the content of 16 components in Zhenwu decoction, refAbstract=null), Reference(id=1243919073176826374, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, doi=null, pmid=null, pmcid=null, year=2021, volume=41, issue=3, pageStart=1798, pageEnd=null, url=null, language=null, rfNumber=[23], rfOrder=39, authorNames=ZHOU W, LIU H, QIU LZ, journalName=Med Res Rev, refType=null, unstructuredReference=ZHOU WLIU HQIU LZet al.Cardiac efficacy and toxicity of aconitine:a new frontier for the ancient poison[J].Med Res Rev202141(3):1798, articleTitle=Cardiac efficacy and toxicity of aconitine:a new frontier for the ancient poison, refAbstract=null)], funds=[Fund(id=1243919068990910939, 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Shandong Kangzhonghong Pharmaceutical Technology Development Co., Ltd, Jinan, 250061, China), AuthorCompanyExt(id=1243919063093719424, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, companyId=1243919063081136510, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.山东康众宏医药科技开发有限公司,济南 250061)])], figs=[ArticleFig(id=1243919067770368463, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=EN, label=Fig. 1, caption=The chromatograms of mixed control solution and sample solution in positive and negative ion modes, figureFileSmall=vrTMJ1iIGivDydkBCU1OfQ==, figureFileBig=7Gf9t/1LQWa+dfWdnVKGow==, tableContent=null), ArticleFig(id=1243919067850060240, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=CN, label=图1, caption=正离子模式、负离子模式下对照品溶液及供试品溶液色谱图

A1、A2:正离子模式下对照品、供试品色谱图(Chromatograms of the reference substance and the test sample in positive ion mode):A. 1.新乌头原碱(mesaconitine) 2.乌头原碱(aconine) 3.附子灵(fuziline) 4.苯甲酰新乌头原碱(benzoylmesaconine) 5.苯甲酰乌头原碱(benzoylaconine)6.苯甲酰次乌头原碱(benzoylhypacoitine) 7.新乌头碱(mesaconine) 8.次乌头碱(hypaconitine) 9.乌头碱(aconitine)B1、B2:负离子模式下对照品、供试品色谱图(Chromatograms of the reference substance and the test sample in negative ion mode.):B. 1.原儿茶酸(protocatechuic acid) 2.夏佛塔苷(schaftoside) 3.异甘草苷(isoliquiritoside) 4.芹糖甘草苷(liquiritin apioside) 5.芹糖异甘草苷(liquiritin apioside)6.甘草苷(liquiritin) 7.甘草查尔酮B(licochalcone B) 8.甘草素(liquiritigenin) 9.柚皮素(naringenin) 10.刺甘草查尔酮(echinatin)11.异甘草素(isoliquiritigenin) 12.甘草酸铵(glycyrrhizic acid ammonium salt) 13.甘草香豆素(glycycoumarin)

, figureFileSmall=vrTMJ1iIGivDydkBCU1OfQ==, figureFileBig=7Gf9t/1LQWa+dfWdnVKGow==, tableContent=null), ArticleFig(id=1243919068042998225, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=EN, label=Fig. 2, caption=The chromatograms of decoction pieces without single flavor in positive and negative ion modes, figureFileSmall=VI8dfx5dFau+V9HCg/nOug==, figureFileBig=51MvqKJVFTQKP/UTcYoAtg==, tableContent=null), ArticleFig(id=1243919068126884306, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=CN, label=图2, caption=正负离子模式下缺单味饮片色谱图

A.缺甘草供试品:A1正离子模式;A2负离子模式(A. Lack of test sample of Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle: A1 positive ion mode;A2 negative ion mode) A. 1.新乌头原碱(mesaconitine) 2.乌头原碱(aconine) 3.附子灵(fuziline) 4.苯甲酰新乌头原碱(benzoylmesaconine) 5.苯甲酰乌头原碱(benzoylaconine) 6.苯甲酰次乌头原碱(benzoylhypacoitine) 7.新乌头碱(mesaconine) 8.次乌头碱(hypaconitine) 9.乌头碱(aconitine)

, figureFileSmall=VI8dfx5dFau+V9HCg/nOug==, figureFileBig=51MvqKJVFTQKP/UTcYoAtg==, tableContent=null), ArticleFig(id=1243919068214964691, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=EN, label=Tab. 1, caption=

Mass spectrum parameters for various constituents

, figureFileSmall=null, figureFileBig=null, tableContent=
峰号
(peak No.)
成分
(component)
tR/min m/z碰撞能量
(collision energy)/eV
母离子
(precuesor ion)
子离子
(product ion)
1原儿茶酸(protocatechuic acid)2.95153.08[M-H]-109.07*14.35
91.03
2新乌头原碱(mesaconine)3.37486.34[M+H]+436.29*33.48
454.22
3乌头原碱(aconine)4.62500.33[M+H]+450.22*34.28
468.21
4附子灵(fuziline)6.07454.39[M+H]+436.29*31.96
404.29
5夏佛塔苷(schaftoside)9.64563.14[M-H]-353.23*34.95
383.50
6甘草苷(liquiritin)10.33417.12[M-H]-255.00*17.13
148.05
7芹糖甘草苷(liquiritin apioside)10.60549.21[M-H]-135.12*43.46
255.12
8苯甲酰新乌头原碱(benzoylmesaconine)12.08590.36[M+H]+540.29*34.65
105.07
9苯甲酰乌头原碱(benzoylaconine)12.93604.38[M+H]+554.29*36.09
105.05
10芹糖异甘草苷(isoliquiritin apioside)13.53549.22[M-H]-255.13*28.00
135.12
11苯甲酰次乌头原碱(benzoylhypacoitine)13.73574.40[M+H]+542.22*33.31
510.23
12异甘草苷(isoliquiritoside)14.03417.20[M-H]-134.88*31.03
119.08
13甘草查尔酮B(licochalcone B)14.68285.06[M-H]-150.13*22.94
270.05
14甘草素(liquiritigenin)14.86255.09[M-H]-134.93*14.86
119.20
15新乌头碱(mesaconitine)16.55632.39[M+H]+572.29*32.59
354.20
16柚皮素(naringenin)18.44271.09[M-H]-151.20*17.3
119.08
17次乌头碱(hypaconitine)18.46616.37[M+H]+524.29*35.88
338.23
18乌头碱(aconitine)18.57646.46[M+H]+526.39*38.95
105.05
19刺甘草查尔酮(echinatin)18.74269.14[M-H]-237.14*17.59
175.35
20异甘草素(isoliquiritigenin)20.56255.06[M-H]-119.17*24.25
135.17
21甘草酸铵(glycyrrhizic acid ammonium salt)20.96821.47[M-H]-350.71*39.96
645.30
22甘草香豆素(glycycoumarin)21.64367.25[M-H]-309.13*25.77
297.05
), ArticleFig(id=1243919068307239380, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=CN, label=表1, caption=

各成分质谱参数

, figureFileSmall=null, figureFileBig=null, tableContent=
峰号
(peak No.)
成分
(component)
tR/min m/z碰撞能量
(collision energy)/eV
母离子
(precuesor ion)
子离子
(product ion)
1原儿茶酸(protocatechuic acid)2.95153.08[M-H]-109.07*14.35
91.03
2新乌头原碱(mesaconine)3.37486.34[M+H]+436.29*33.48
454.22
3乌头原碱(aconine)4.62500.33[M+H]+450.22*34.28
468.21
4附子灵(fuziline)6.07454.39[M+H]+436.29*31.96
404.29
5夏佛塔苷(schaftoside)9.64563.14[M-H]-353.23*34.95
383.50
6甘草苷(liquiritin)10.33417.12[M-H]-255.00*17.13
148.05
7芹糖甘草苷(liquiritin apioside)10.60549.21[M-H]-135.12*43.46
255.12
8苯甲酰新乌头原碱(benzoylmesaconine)12.08590.36[M+H]+540.29*34.65
105.07
9苯甲酰乌头原碱(benzoylaconine)12.93604.38[M+H]+554.29*36.09
105.05
10芹糖异甘草苷(isoliquiritin apioside)13.53549.22[M-H]-255.13*28.00
135.12
11苯甲酰次乌头原碱(benzoylhypacoitine)13.73574.40[M+H]+542.22*33.31
510.23
12异甘草苷(isoliquiritoside)14.03417.20[M-H]-134.88*31.03
119.08
13甘草查尔酮B(licochalcone B)14.68285.06[M-H]-150.13*22.94
270.05
14甘草素(liquiritigenin)14.86255.09[M-H]-134.93*14.86
119.20
15新乌头碱(mesaconitine)16.55632.39[M+H]+572.29*32.59
354.20
16柚皮素(naringenin)18.44271.09[M-H]-151.20*17.3
119.08
17次乌头碱(hypaconitine)18.46616.37[M+H]+524.29*35.88
338.23
18乌头碱(aconitine)18.57646.46[M+H]+526.39*38.95
105.05
19刺甘草查尔酮(echinatin)18.74269.14[M-H]-237.14*17.59
175.35
20异甘草素(isoliquiritigenin)20.56255.06[M-H]-119.17*24.25
135.17
21甘草酸铵(glycyrrhizic acid ammonium salt)20.96821.47[M-H]-350.71*39.96
645.30
22甘草香豆素(glycycoumarin)21.64367.25[M-H]-309.13*25.77
297.05
), ArticleFig(id=1243919068399514069, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=EN, label=Tab. 2, caption=

Linear investigation results

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)
线性方程
(calibration curve)
R2线性范围
(liner range)/(ng · mL-1
LOD/(ng · mL-1LOQ/(ng · mL-1
原儿茶酸(protocatechuic acid) Y=3 846.6X+2 440.580.998 40.836~107.0000.420.84
乌头原碱(aconine) Y=1 894.83X-3 421.130.999 82.266~580.0002.002.27
附子灵(fuziline) Y=5 013.42X+151 0830.999 70.898~11 500.0000.200.40
夏佛塔苷(schaftoside) Y=841.439X+8 802.740.999 80.805~824.0000.100.20
芹糖甘草苷(liquiritin apioside) Y=513.258X+41 761.90.999 81.259~20 625.0000.080.66
甘草苷(liquiritin) Y=2 692.33X+304 9910.999 00.820~15 120.0000.050.10
苯甲酰新乌头原碱(benzoylmesaconine) Y=2 598.46X+118 7320.999 71.516~15 520.0000.100.65
苯甲酰乌头原碱(benzoylaconine) Y=2 921.6X-18 988.20.999 21.578~808.0000.101.30
芹糖异甘草苷(liquiritin apioside) Y=590.585X+149 4800.996 60.629~20 625.0000.030.05
苯甲酰次乌头原碱(benzoylhypacoitine) Y=7 094.16X-29 329.40.999 60.813~832.0000.070.10
异甘草苷(isoliquiritoside) Y=799.768X+282 1870.997 03.406~50 000.0000.843.38
甘草查尔酮B(licochalcone B) Y=4 617X-34 914.40.998 31.609~824.0000.410.82
甘草素(liquiritigenin) Y=2 954.64X+128 8380.999 60.789~10 100.0000.040.10
新乌头原碱(mesaconine) Y=1 011.8X+19543.80.999 14.688~4 800.0000.594.69
柚皮素(naringenin) Y=1 987.61X-3 220.280.999 50.891~228.0000.891.00
刺甘草查尔酮(echinatin) Y=2 187.57X+13 546.70.999 30.813~832.0000.200.60
异甘草素(isoliquiritigenin) Y=196.887X+1 588.740.999 03.438~880.0001.723.00
甘草酸铵(glycyrrhizic acid ammonium salt) Y=77.053 8X+57 7850.999 21.526~100 000.0000.040.07
甘草香豆素(glycycoumarin) Y=16 175.7X+118 8000.999 00.852~872.0000.010.03
次乌头碱(hypaconitine) Y=3 198.98X-3 478.190.999 61.914~122.5000.981.91
乌头碱(aconitine) Y=5 964.21X+1 801.040.999 50.220~112.5000.120.15
新乌头碱(mesaconitine) Y=3 997.46X-3 954.520.999 71.379~88.2810.501.38
), ArticleFig(id=1243919068483400150, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=CN, label=表2, caption=

线性考察结果

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)
线性方程
(calibration curve)
R2线性范围
(liner range)/(ng · mL-1
LOD/(ng · mL-1LOQ/(ng · mL-1
原儿茶酸(protocatechuic acid) Y=3 846.6X+2 440.580.998 40.836~107.0000.420.84
乌头原碱(aconine) Y=1 894.83X-3 421.130.999 82.266~580.0002.002.27
附子灵(fuziline) Y=5 013.42X+151 0830.999 70.898~11 500.0000.200.40
夏佛塔苷(schaftoside) Y=841.439X+8 802.740.999 80.805~824.0000.100.20
芹糖甘草苷(liquiritin apioside) Y=513.258X+41 761.90.999 81.259~20 625.0000.080.66
甘草苷(liquiritin) Y=2 692.33X+304 9910.999 00.820~15 120.0000.050.10
苯甲酰新乌头原碱(benzoylmesaconine) Y=2 598.46X+118 7320.999 71.516~15 520.0000.100.65
苯甲酰乌头原碱(benzoylaconine) Y=2 921.6X-18 988.20.999 21.578~808.0000.101.30
芹糖异甘草苷(liquiritin apioside) Y=590.585X+149 4800.996 60.629~20 625.0000.030.05
苯甲酰次乌头原碱(benzoylhypacoitine) Y=7 094.16X-29 329.40.999 60.813~832.0000.070.10
异甘草苷(isoliquiritoside) Y=799.768X+282 1870.997 03.406~50 000.0000.843.38
甘草查尔酮B(licochalcone B) Y=4 617X-34 914.40.998 31.609~824.0000.410.82
甘草素(liquiritigenin) Y=2 954.64X+128 8380.999 60.789~10 100.0000.040.10
新乌头原碱(mesaconine) Y=1 011.8X+19543.80.999 14.688~4 800.0000.594.69
柚皮素(naringenin) Y=1 987.61X-3 220.280.999 50.891~228.0000.891.00
刺甘草查尔酮(echinatin) Y=2 187.57X+13 546.70.999 30.813~832.0000.200.60
异甘草素(isoliquiritigenin) Y=196.887X+1 588.740.999 03.438~880.0001.723.00
甘草酸铵(glycyrrhizic acid ammonium salt) Y=77.053 8X+57 7850.999 21.526~100 000.0000.040.07
甘草香豆素(glycycoumarin) Y=16 175.7X+118 8000.999 00.852~872.0000.010.03
次乌头碱(hypaconitine) Y=3 198.98X-3 478.190.999 61.914~122.5000.981.91
乌头碱(aconitine) Y=5 964.21X+1 801.040.999 50.220~112.5000.120.15
新乌头碱(mesaconitine) Y=3 997.46X-3 954.520.999 71.379~88.2810.501.38
), ArticleFig(id=1243919068571480535, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=EN, label=Tab. 3, caption=

Dosing recovery results

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)
供试品含量
(conteent)/ng
加入量
(added)/ng
测得量
(measured)/ng
回收率
(recovery)/%
RSD/%
原儿茶酸(protocatechuic acid)571.96575.531 151.12100.62.0
乌头原碱(aconine)4 410.814 457.238 716.4196.62.2
附子灵(fuziline)25 389.9226 541.3853 130.80104.53.5
夏佛塔苷(schaftoside)6 716.197 020.1914 049.37104.51.8
芹糖甘草苷(liquiritin apioside)66 130.7867 235.81134 682.62102.01.5
甘草苷(liquiritin)12 310.2012 919.6825 841.70104.70.93
苯甲酰新乌头原碱(benzoylmesaconine)41 534.1442 318.5284 210.62100.91.2
苯甲酰乌头原碱(benzoylaconine)4 080.283 912.237 828.1595.83.7
芹糖异甘草苷(liquiritin apioside)48 994.8151 517.81101 902.48102.73.9
苯甲酰次乌头原碱(benzoylhypacoitine)8 400.118 258.4316 518.7798.32.8
异甘草苷(isoliquiritoside)564 325.23565 085.981 131 515.91100.40.34
甘草查尔酮B(licochalcone B)3 711.193 604.767 237.8697.81.2
甘草素(liquiritigenin)12121.1812 815.1024 876.0299.54.1
新乌头原碱(mesaconine)50 745.0150 970.72100 699.4098.01.3
柚皮素(naringenin)1 116.641 112.432 225.3499.73.2
刺甘草查尔酮(echinatin)1 220.011 334.642 613.45104.411.4
异甘草素(isoliquiritigenin)4 317.074 499.589 002.23104.14.7
甘草酸铵(glycyrrhizic acid ammonium salt)1 121 932.111 107 179.842 207 107.6898.01.7
甘草香豆素(glycycoumarin)1 742.681 772.453 576.25103.51.5
次乌头碱(hypaconitine)1 005.49983.411 966.9697.80.54
乌头碱(aconitine)4.358.7513.52104.82.6
新乌头碱(mesaconitine)94.7190.66185.2999.91.9
), ArticleFig(id=1243919068646978008, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=CN, label=表3, caption=

加样回收率考察结果

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)
供试品含量
(conteent)/ng
加入量
(added)/ng
测得量
(measured)/ng
回收率
(recovery)/%
RSD/%
原儿茶酸(protocatechuic acid)571.96575.531 151.12100.62.0
乌头原碱(aconine)4 410.814 457.238 716.4196.62.2
附子灵(fuziline)25 389.9226 541.3853 130.80104.53.5
夏佛塔苷(schaftoside)6 716.197 020.1914 049.37104.51.8
芹糖甘草苷(liquiritin apioside)66 130.7867 235.81134 682.62102.01.5
甘草苷(liquiritin)12 310.2012 919.6825 841.70104.70.93
苯甲酰新乌头原碱(benzoylmesaconine)41 534.1442 318.5284 210.62100.91.2
苯甲酰乌头原碱(benzoylaconine)4 080.283 912.237 828.1595.83.7
芹糖异甘草苷(liquiritin apioside)48 994.8151 517.81101 902.48102.73.9
苯甲酰次乌头原碱(benzoylhypacoitine)8 400.118 258.4316 518.7798.32.8
异甘草苷(isoliquiritoside)564 325.23565 085.981 131 515.91100.40.34
甘草查尔酮B(licochalcone B)3 711.193 604.767 237.8697.81.2
甘草素(liquiritigenin)12121.1812 815.1024 876.0299.54.1
新乌头原碱(mesaconine)50 745.0150 970.72100 699.4098.01.3
柚皮素(naringenin)1 116.641 112.432 225.3499.73.2
刺甘草查尔酮(echinatin)1 220.011 334.642 613.45104.411.4
异甘草素(isoliquiritigenin)4 317.074 499.589 002.23104.14.7
甘草酸铵(glycyrrhizic acid ammonium salt)1 121 932.111 107 179.842 207 107.6898.01.7
甘草香豆素(glycycoumarin)1 742.681 772.453 576.25103.51.5
次乌头碱(hypaconitine)1 005.49983.411 966.9697.80.54
乌头碱(aconitine)4.358.7513.52104.82.6
新乌头碱(mesaconitine)94.7190.66185.2999.91.9
), ArticleFig(id=1243919068730864089, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=EN, label=Tab. 4, caption=

The content of 22 components in the three batches of Bimin capsules

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)
含量(content)(μg · g-1来源
(source)
BMJN-01BMJN-02BMJN-03
原儿茶酸(protocatechuic acid)12.4614.8914.26炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
乌头原碱(aconine)85.3998.1689.23黑顺片(Aconiti Lateralis Radix Praeparata)
附子灵(fuziline)720.79814.85726.81黑顺片(Aconiti Lateralis Radix Praeparata)
夏佛塔苷(schaftoside)99.96107.18109.87炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
芹糖甘草苷(liquiritin apioside)1 196.381 451.221 378.40炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草苷(liquiritin)242.68243.75239.15炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
苯甲酰新乌头原碱(benzoylmesaconine)781.22807.33820.72黑顺片(Aconiti Lateralis Radix Praeparata)
苯甲酰乌头原碱(benzoylaconine)80.68128.85106.77黑顺片(Aconiti Lateralis Radix Praeparata)
芹糖异甘草苷(liquiritin apioside)1 016.171 005.44994.46炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
苯甲酰次乌头原碱(benzoylhypacoitine)175.90172.53139.29黑顺片(Aconiti Lateralis Radix Praeparata)
异甘草苷(isoliquiritoside)10 138.7011 480.2911 527.48炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草查尔酮B(licochalcone B)78.0984.0069.78炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草素(liquiritigenin)243.61192.18221.41炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
新乌头原碱(mesaconine)1 049.271 090.95997.83黑顺片(Aconiti Lateralis Radix Praeparata)
柚皮素(naringenin)27.8723.6530.71炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
刺甘草查尔酮(echinatin)26.5027.9930.47炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
异甘草素(isoliquiritigenin)92.2091.6961.97炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草酸铵(glycyrrhizic acid ammonium salt)22 442.4422 877.0323 505.37炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草香豆素(glycycoumarin)36.5868.2773.21炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
次乌头碱(hypaconitine)19.6420.1722.97黑顺片(Aconiti Lateralis Radix Praeparata)
乌头碱(aconitine)0.060.060.07黑顺片(Aconiti Lateralis Radix Praeparata)
新乌头碱(mesaconitine)1.712.042.38黑顺片(Aconiti Lateralis Radix Praeparata)
), ArticleFig(id=1243919068818944474, tenantId=1146029695717560320, journalId=1205117023404326918, articleId=1240709664451654197, language=CN, label=表4, caption=

3批鼻敏胶囊中22个成分的含量(n=2)

, figureFileSmall=null, figureFileBig=null, tableContent=
成分
(component)
含量(content)(μg · g-1来源
(source)
BMJN-01BMJN-02BMJN-03
原儿茶酸(protocatechuic acid)12.4614.8914.26炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
乌头原碱(aconine)85.3998.1689.23黑顺片(Aconiti Lateralis Radix Praeparata)
附子灵(fuziline)720.79814.85726.81黑顺片(Aconiti Lateralis Radix Praeparata)
夏佛塔苷(schaftoside)99.96107.18109.87炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
芹糖甘草苷(liquiritin apioside)1 196.381 451.221 378.40炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草苷(liquiritin)242.68243.75239.15炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
苯甲酰新乌头原碱(benzoylmesaconine)781.22807.33820.72黑顺片(Aconiti Lateralis Radix Praeparata)
苯甲酰乌头原碱(benzoylaconine)80.68128.85106.77黑顺片(Aconiti Lateralis Radix Praeparata)
芹糖异甘草苷(liquiritin apioside)1 016.171 005.44994.46炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
苯甲酰次乌头原碱(benzoylhypacoitine)175.90172.53139.29黑顺片(Aconiti Lateralis Radix Praeparata)
异甘草苷(isoliquiritoside)10 138.7011 480.2911 527.48炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草查尔酮B(licochalcone B)78.0984.0069.78炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草素(liquiritigenin)243.61192.18221.41炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
新乌头原碱(mesaconine)1 049.271 090.95997.83黑顺片(Aconiti Lateralis Radix Praeparata)
柚皮素(naringenin)27.8723.6530.71炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
刺甘草查尔酮(echinatin)26.5027.9930.47炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
异甘草素(isoliquiritigenin)92.2091.6961.97炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草酸铵(glycyrrhizic acid ammonium salt)22 442.4422 877.0323 505.37炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
甘草香豆素(glycycoumarin)36.5868.2773.21炙甘草(Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle)
次乌头碱(hypaconitine)19.6420.1722.97黑顺片(Aconiti Lateralis Radix Praeparata)
乌头碱(aconitine)0.060.060.07黑顺片(Aconiti Lateralis Radix Praeparata)
新乌头碱(mesaconitine)1.712.042.38黑顺片(Aconiti Lateralis Radix Praeparata)
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UPLC-MS/MS法同时测定鼻敏胶囊中22个成分的含量*
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曹蕾 1, 2 , 毕建云 1 , 王玉清 2, ** , 张新军 2 , 苏酩 2, 1 , 王博阳 2 , 李鑫蕊 2 , 孙新茹 2 , 肖康宁 2 , 侯玉洁 1, 2 , 刘圣梅 3 , 周倩 2 , 刘善新 2, **
药物分析杂志 | 成分分析 2025,45(3): 400-408
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药物分析杂志 | 成分分析 2025, 45(3): 400-408
UPLC-MS/MS法同时测定鼻敏胶囊中22个成分的含量*
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曹蕾1, 2 , 毕建云1, 王玉清2, ** , 张新军2, 苏酩2, 1, 王博阳2, 李鑫蕊2, 孙新茹2, 肖康宁2, 侯玉洁1, 2, 刘圣梅3, 周倩2, 刘善新2, **
作者信息
  • 1.山东中医药大学,济南 250355
  • 2.山东省中医药研究院,济南 250014
  • 3.山东康众宏医药科技开发有限公司,济南 250061
  • Tel:17852752632;E-mail:

通讯作者:

**王玉清 Tel:(0531)82949813;E-mail:;
刘善新 Tel:(0531)82949813;E-mail:
Simultaneou determination of 22 components in Bimin capsules by UPLC-MS/MS*
Lei CAO1, 2 , Jian-yun BI1, Yu-qing WANG2, ** , Xin-jun ZHANG2, Ming SU2, 1, Bo-yang WANG2, Xin-rui LI2, Xin-ru SUN2, Kang-ning XIAO2, Yu-jie HOU1, 2, Sheng-mei LIU3, Qian ZHOU2, Shan-xin LIU2, **
Affiliations
  • 1. Shandong University of Chinese Medicine, Jinan 250355, China
  • 2. Shandong Academy of Traditional Chinese Medicine,Jinan 250014, China
  • 3. Shandong Kangzhonghong Pharmaceutical Technology Development Co., Ltd, Jinan, 250061, China
出版时间: 2025-03-31 doi: 10.16155/j.0254-1793.2024-0395
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目的:建立超高效液相色谱串联质谱(UPLC-MS/MS)方法同时测定鼻敏胶囊样品中苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱、次乌头碱、新乌头碱、附子灵、乌头碱、乌头原碱、新乌头原碱、异甘草素、刺甘草查尔酮、原儿茶酸、甘草素、异甘草苷、甘草香豆素、柚皮素、夏佛塔苷、甘草查尔酮B、甘草酸铵、甘草苷、芹糖甘草苷、芹糖异甘草苷22个成分的含量。方法:采用AcclaimTM RSLC 120C18型色谱柱(2.1 mm×100 mm,2.2 μm),以0.05%甲酸水(A)-乙腈(B)为流动相,梯度洗脱,流速为0.4 mL · min-1;采用电喷雾离子源(ESI)、多反应检测(MRM)模式进行正、负离子检测。结果:22个成分在各自的范围内线性关系良好(R2>0.990),精密度、重复性、稳定性、加样回收率等均符合要求。结果发现,22个成分在鼻敏胶囊中均被检测到,个别成分含量相差较大。结论:该方法快速、简便、灵敏、可靠,可为鼻敏胶囊的质量控制提供科学依据。

鼻敏胶囊  /  化学成分  /  超高效液相色谱-三重四极杆质谱联用法  /  含量测定  /  变应性鼻炎

Objective: To establish an ultra-high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method for the simultaneous determination of 22 components of Bimin capsules, including benzoylaconine, benzoylmesaconine, benzoylhypacoitine, hypaconitine, mesaconitine, fuziline, aconitine, aconine,mesaconine, isoliquiritigenin, echinatin, protocatechuic acid, liquiritigenin, isoliquiritoside, glycycoumarin,naringenin, schaftoside, licochalcone B, glycyrrhizic acid ammonium salt, liquiritin, liquiritin apioside and isoliquiritin apioside. Methods: The AcclaimTM RSLC 120C18 column (2.1 mm×100 mm, 2.2 μm) was used with 0.05% formic acid water (A) and acetonitrile (B) as the mobile phase at a flow rate of 0.4 mL · min-1. Electrospray ionization (ESI) source and multiple reaction monitoring (MRM) mode in both positive and negative were used for ion detections. Resulets:The 22 components displayed a good linear relationship (R2>0.990) in their respective ranges, and the precision, repeatability, stability, and sample recovery rate all met the requirements. It was found that all 22 components were detected in the nasal sensitivity capsules, with significant differences in the content of some components. Conclusion: This method is fast, simple, sensitive and reliable, and can provide scientific basis for the quality control of the Bimin capsules.

Bimin capsules  /  chemical composition  /  UPLC-MS/MS  /  content determination  /  allergic rhinitis
曹蕾, 毕建云, 王玉清, 张新军, 苏酩, 王博阳, 李鑫蕊, 孙新茹, 肖康宁, 侯玉洁, 刘圣梅, 周倩, 刘善新. UPLC-MS/MS法同时测定鼻敏胶囊中22个成分的含量*. 药物分析杂志, 2025 , 45 (3) : 400 -408 . DOI: 10.16155/j.0254-1793.2024-0395
Lei CAO, Jian-yun BI, Yu-qing WANG, Xin-jun ZHANG, Ming SU, Bo-yang WANG, Xin-rui LI, Xin-ru SUN, Kang-ning XIAO, Yu-jie HOU, Sheng-mei LIU, Qian ZHOU, Shan-xin LIU. Simultaneou determination of 22 components in Bimin capsules by UPLC-MS/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2025 , 45 (3) : 400 -408 . DOI: 10.16155/j.0254-1793.2024-0395
鼻敏胶囊是中药Ⅰ类创新药,由黑顺片、炙甘草等组成,具有温肾散寒、暖肺通窍的功效,临床上用于治疗变应性鼻炎(allergic rhinitis,AR)。该方由经典名方“四逆汤”去干姜而成,原方主要治疗脾肾阳虚,阴寒内盛的四肢厥逆证[1],附子配干姜意在增强回心阳之力,过敏性鼻炎非亡阳之证,无需急温之,只需温肾升阳,缓缓图功,考虑附子配干姜大热,故去干姜,体现了《内经》中的“少火生气”的思想[2];甘草性甘、平,可调和药性,抑制附片的辛热燥烈之性,去其邪性,留其正性,以便更好地发挥其药理作用[2-4]。现代药理学研究表明,附子和甘草在抗炎、抗过敏、免疫调节等方面疗效显著[5-8],已有研究表明,口服去甲乌头碱能显著降低卵白蛋白所诱导的AR小鼠血清中IgE、组胺和IL-4的水平,调节Th 1/Th 2细胞的失衡[9]。甘草提取物鼻腔灌洗给药治疗AR患者具有明显的疗效且无副作用[10],甘草酸能逆转组胺对人鼻上皮细胞中呼吸道黏蛋白(MUC5AC)表达、炎症细胞因子产生和水通道蛋白(AQP5)表达的影响[11]
鼻敏胶囊处于临床研究阶段,物质基础研究薄弱,处方成分含量不明确。目前,超高效液相色谱串联质谱(UPLC-MS/MS)法越来越多地应用于中药复方的分析,因其具有良好的灵敏度和专属性,故常用于中药复方多成分的质量控制[12-14]。基于此,本研究采用UPLC-MS/MS对鼻敏胶囊中22个成分进行含量测定,为鼻敏胶囊的质量控制提供参考,并为其药效物质研究奠定基础。
Thermo Scientific Vanquish 超高效液相色谱仪;TSQ Quantum三重四极杆质谱仪(Thermo Fisher Scientific);AcclaimTM RSLC 120C18型色谱柱(2.1 mm×100 mm,2.2 μm,Thermo Fisher Scientific);KQ-250DA型数控超声波清洗器(昆山市超声仪器有限公司);AE224C型万分之一电子天平(上海舜宇恒平科学仪器有限公司);MS105十万分之一电子天平(METTLER TOLEDO公司);Milli-QIQ7000超纯水机(MERCK,德国)。
对照品苯甲酰乌头原碱(批号PS011883,纯度>98.0%)、苯甲酰新乌头原碱(批号PS010496,纯度>98.0%)、苯甲酰次乌头原碱(批号PS011884,纯度>98.0%)、次乌头碱(批号PS010300,纯度>98.0%)、新乌头碱(批号PS010171,纯度≥98.5%)、异甘草素(批号PS001032,纯度>98.0%)、刺甘草查尔酮(批号PS000688,纯度>98.0%)、原儿茶酸(批号PS012560,纯度100%)、甘草素(批号PS010083,纯度>98.0%)、乌头原碱(批号PS011831,纯度≥98.5%)、新乌头原碱(批号PS013220,纯度≥98.0%)、附子灵(批号PS020826,纯度≥98.0%)、异甘草苷(批号PS012517,纯度≥98.5%)、甘草香豆素(批号PS012475,纯度≥98.0%)、柚皮素(批号PS010691,纯度≥99.0%)、芹糖异甘草苷(批号PS012516,纯度99.87%)、夏佛塔苷(批号PS012525,纯度97.7%)、甘草查尔酮B(批号PS011558,纯度≥98.0%)购自成都普思生物科技股份有限公司,甘草酸铵(批号110731-201720,纯度97.7%)、甘草苷(批号111610-201908,纯度95.0%)购自中国食品药品检定研究院,芹糖甘草苷(批号PRF9050224,纯度98.0%)购自成都普瑞法科技开发有限公司,乌头碱(批号23030417,纯度98.61%)购自北京中科质检生物技术有限公司。黑顺片(批号230701),四川江油鑫临附子药业有限公司;炙甘草(批号C577230502),河北鹤州药业有限公司;黑顺片、炙甘草饮片由山东省中医药研究院靳光乾主任药师鉴定;鼻敏胶囊(批号:BMJN-01、BMJN-02、BMJN-03),由本课题组制备;乙腈、甲醇、甲酸为质谱纯(Thermo Fisher);纯净水(超纯水机制备)。
色谱柱为AcclaimTM RSLC 120 C18型色谱柱(2.1 mm×100 mm,2.2 μm),流动相为0.05%甲酸水(A)-乙腈(B),梯度洗脱(0~7 min,5%B→12%B;7~8 min,12%B→17%B;8~11 min,17%B→22%B,11~17 min,22%B→28%B;17~17.5 min,28%B→32%B;17.5~19 min,32%B→35%B;19~21 min,35%B→65%B;21~24 min,65%B→80%B),流速为0.4 mL · min-1,柱温为30 ℃,进样量为3 μL。
离子源为电喷雾离子源(ESI),正负离子检测;多反应监测(MRM)模式;正离子模式毛细管电压为3 500 V,负离子模式为-3 000 V,毛细管温度350 ℃,汽化温度320 ℃,鞘气和辅助气均为氮气,鞘气流速为40 arb,辅助气流速为10 arb,质谱参数详见表1
表1中的22个对照品适量,精密称定,加入乙腈制备乌头碱对照品储备液,其余各对照品储备液加入甲醇制备。各对照品质量浓度分别为原儿茶酸107 μg · mL-1、芹糖异甘草苷82.5 μg · mL-1、异甘草素110 μg · mL-1、柚皮素114 μg · mL-1、甘草素101 μg · mL-1、异甘草苷109 μg · mL-1、甘草香豆素109 μg · mL-1、甘草酸铵110 μg · mL-1、甘草苷105 μg · mL-1、夏佛塔苷103 μg · mL-1、甘草查尔酮B 103 μg · mL-1、刺甘草查尔酮104 μg · mL-1、芹糖甘草苷82.5 μg · mL-1、附子灵115 μg · mL-1、乌头原碱145 μg · mL-1、新乌头原碱96 μg · mL-1、苯甲酰新乌头原碱194 μg · mL-1、苯甲酰次乌头原碱208 μg · mL-1、苯甲酰乌头原碱202 μg · mL-1、新乌头碱226 μg · mL-1、次乌头碱196 μg · mL-1、乌头碱180 μg · mL-1。取甘草酸铵储备液用甲醇稀释至100 μg · mL-1,得单一对照品溶液,取原儿茶酸、异甘草素、柚皮素、甘草素、异甘草苷、甘草香豆素、甘草苷、甘草查尔酮B、刺甘草查尔酮、夏佛塔苷、附子灵、乌头原碱、苯甲酰次乌头原碱、苯甲酰乌头原碱、乌头碱的对照品储备液各1 mL至25 mL量瓶中,取新乌头原碱、新乌头碱次乌头碱、苯甲酰新乌头原碱的对照品储备液各1 mL至10 mL量瓶中,取芹糖甘草苷、芹糖异甘草苷的对照品储备液各1 mL至2 mL量瓶中,分别加入甲醇定容,摇匀,得各混合对照品溶液。
取鼻敏胶囊内容物适量,研细,称取0.1 g,精密称定,精密加入甲醇25 mL,密塞,称定,超声(250 W,40 kHz)30 min,取出放冷再称定,用甲醇补足减失的量,摇匀,过0.22 μm微孔滤膜滤过,取续滤液,即得。
取“2.3”项下各混合对照品溶液、“2.4”项下供试品溶液以及空白溶剂(甲醇),在“2.1”项色谱条件和“2.2”项质谱条件下进样分析,供试品溶液中22个被测成分与对照品的保留时间相同。被测定成分分离效果良好,无其他干扰,比较各测定成分和对照品的色谱图,见图1,供试品溶液与对照品溶液在相同保留时间出现相应色谱峰,且空白溶剂无干扰;单味药材阴性溶液对照色谱图见图2
取“2.3”项下配制的单一对照品溶液及混合对照品储备液适量,逐级稀释,即得标准曲线各质量浓度点的系列对照品溶液。按照“2.1”项下色谱条件和“2.2”项下质谱条件进行测定,结果见表2,22个成分在各自的质量浓度范围内线性良好。
取“2.3”项下混合对照品溶液,在“2.1”项色谱条件和“2.2”项质谱条件下,连续进样6次测定峰面积,并计算RSD,结果显示原儿茶酸、新乌头原碱、乌头原碱、附子灵、夏佛塔苷、甘草苷、芹糖甘草苷、苯甲酰新乌头原碱、苯甲酰乌头原碱、芹糖异甘草苷、苯甲酰次乌头原碱、异甘草苷、甘草查尔酮B、甘草素、新乌头碱、柚皮素、次乌头碱、乌头碱、刺甘草查尔酮、异甘草素、甘草酸铵和甘草香豆素峰面积的RSD分别为0.32%、1.2%、0.51%、0.34%、0.66%、0.43%、0.29%、0.63%、0.18%、0.41%、0.91%、1.7%、0.33%、1.3%、1.2%、0.13%、1.7%、5.1%、0.28%、0.24%、1.8%和0.55%。
取BMJN-01样品,平行制备6份鼻敏胶囊供试品溶液,按照“2.1”项下色谱条件和“2.2”项下质谱条件进行测定,根据峰面积计算各成分含量,并计算RSD。结果显示,原儿茶酸、新乌头原碱、乌头原碱、附子灵、夏佛塔苷、甘草苷、芹糖甘草苷、苯甲酰新乌头原碱、苯甲酰乌头原碱、芹糖异甘草苷、苯甲酰次乌头原碱、异甘草苷、甘草查尔酮B、甘草素、新乌头碱、柚皮素、次乌头碱、乌头碱、刺甘草查尔酮、异甘草素、甘草酸铵和甘草香豆素含量分别为12.1、1024.0、86.9、711.2、117.0、225.4、1343.0、846.4、93.5、1057.3、171.3、11013.3、82.8、247.5、1.9、21.1、19.3、0.1、27.1、96.1、22352.7、35.9 μg·g-1,RSD分别为2.4%、1.7%、1.8%、1.3%、2.0%、3.4%、0.61%、0.70%、1.7%、3.0%、1.3%、0.99%、1.6%、0.32%、1.1%、1.0%、1.4%、2.5%、2.3%、1.2%、0.65%和1.5%。
取同一供试品溶液(BMJN-01),按照“2.1”项下色谱条件和“2.2”项下质谱条件分别于0、1、2、4、6、8、12、24 h进样分析,计算得到各成分的RSD。结果显示,原儿茶酸、新乌头原碱、乌头原碱、附子灵、夏佛塔苷、甘草苷、芹糖甘草苷、苯甲酰新乌头原碱、苯甲酰乌头原碱、芹糖异甘草苷、苯甲酰次乌头原碱、异甘草苷、甘草查尔酮B、甘草素、新乌头碱、柚皮素、次乌头碱、乌头碱、刺甘草查尔酮、异甘草素、甘草酸铵和甘草香豆素峰面积的RSD分别为1.4%、2.9%、0.99%、1.4%、1.4%、1.3%、1.5%、1.5%、0.93%、1.9%、1.3%、1.3%、2.1%、3.4%、3.5%、4.5%、4.1%、5.9%、1.7%、2.6%、2.9%和2.2%。
取含量已知的鼻敏胶囊(BMJN-01)0.05 g,研细,平行称定6份,加入含与所取胶囊粉末各成分含量大致相等的对照品溶液,按“2.4”项方法制备供试溶液,在“2.1”项色谱条件和“2.2”项质谱条件下进行测定,计算加样回收率及其RSD。结果见表3
按照“2.4”项下方法制备鼻敏胶囊供试品溶液,并按照“2.1”项下色谱条件和“2.2”项下质谱条件进样分析,计算各成分含量。结果如表4所示。
在进行测定成分选择时,首先将 2020 年版《中华人民共和国药典》一部[15]中指标成分甘草苷、甘草酸铵、苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、新乌头碱、次乌头碱、乌头碱纳入含量测定范围。另根据前期基于UPLC-Q Exactive Orbitrap MS对鼻敏胶囊化学成分进行的全面分析以及结合相关文献检索,在摸索各待测成分含量的离子对后,最终确定22个成分作为待测成分,且22个成分在抗炎、抗过敏、舒张血管、抗氧化、镇痛、镇咳平喘、免疫调节等方面具有显著药理活性,这对于治疗变应性鼻炎具有良好的作用。
本实验采用超声提取法,操作简便快速,增加溶剂渗透,加快了组分在溶剂中的溶解速度,提高了提取效率[16]。本方由黑顺片及炙甘草组成,成分大多为黄酮类、二萜类及生物碱类成分,综合考虑上述待测成分的溶解性,对提取溶剂(70%甲醇水、甲醇)、样品的称样量(0.1、0.3 g)进行考察,确定最优提取条件为0.1 g鼻敏胶囊粉末加入25 mL甲醇超声(250 W,40 kHz)提取30 min;考察了不同体积分数的甲酸(0.1%甲酸水-乙腈、0.05%甲酸水-乙腈)对分离效果的影响,发现后者洗脱时各成分色谱峰响应提高,峰形更对称;考察了体积流量(0.3、0.4 mL · min-1)、柱温(25、30、35 ℃),发现在0.4 mL · min-1、30 ℃下洗脱时间短,各成分色谱峰峰形良好。经查阅文献及UPLC-Q Exactive Orbitrap MS分析结果,甘草中的化学成分在正、负离子模式下均有响应[17-20],黑顺片中化学成分在正离子模式下响应较好[21-22],故采用正负离子同时检测。
黑顺片中双酯型生物碱为限量检查成分。考虑到乌头碱口服0.2 mg即可发生中毒反应[23],3批鼻敏胶囊样品中双酯型生物碱新乌头碱、乌头碱、次乌头碱的每粒含量分别为8.56、8.90、10.16 μg,3批鼻敏胶囊样品中双酯型生物碱的日服用量范围为77.08~91.51 μg,低于0.2 mg,表明在该剂量下常规用药合理、安全。3批鼻敏胶囊中苯甲酰乌头原碱、苯甲酰次乌头原碱、苯甲酰新乌头原碱每粒含量分别为415.12、443.48、426.71 μg,每粒含量范围在415.12~443.48 μg,含量较为稳定,可以为鼻敏胶囊质量标准的完善提供参考。
本实验建立了UPLC-MS/MS法同时测定鼻敏胶囊中苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱、次乌头碱、新乌头碱、异甘草素、刺甘草查尔酮、原儿茶酸、甘草素、附子灵、乌头碱、乌头原碱、新乌头原碱、异甘草苷、甘草香豆素、柚皮素、夏佛塔苷、甘草查尔酮B、甘草酸铵、甘草苷、芹糖甘草苷、芹糖异甘草苷共22个成分的含量,可为该制剂质量控制提供理论依据。
  • 山东中医药科技项目(Q-2023179)
  • 山东中医药科技项目(Q-2023022)
  • 山东中医药科技项目(Q-2023169)
  • 山东省新旧动能转换重大工程重大课题攻关项目(202006)
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doi: 10.16155/j.0254-1793.2024-0395
  • 接收时间:2024-06-14
  • 首发时间:2026-03-17
  • 出版时间:2025-03-31
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  • 收稿日期:2024-06-14
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山东中医药科技项目(Q-2023179)
山东中医药科技项目(Q-2023022)
山东中医药科技项目(Q-2023169)
山东省新旧动能转换重大工程重大课题攻关项目(202006)
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    1.山东中医药大学,济南 250355
    2.山东省中医药研究院,济南 250014
    3.山东康众宏医药科技开发有限公司,济南 250061

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占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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