经典名方易黄汤物质基准HPLC特征图谱的建立及量值传递研究

李华露; 李秋桐; 刘华兰; 刘陶世; 嵇晶; 程建明; 郭青

doi:10.14148/j.issn.1672-0482.2022.0621

经典名方易黄汤物质基准HPLC特征图谱的建立及量值传递研究

doi: 10.14148/j.issn.1672-0482.2022.0621

李华露^{1, 2,},
李秋桐^{1, 2},
刘华兰^{1, 2},
刘陶世^{1, 2},
嵇晶^{1, 2},
程建明^{1, 2, ,},
郭青³

1.
南京中医药大学药学院, 江苏南京 210023
2.
江苏省经典名方工程研究中心, 江苏南京 210023
3.
江苏省食品药品监督检验研究院, 江苏南京 210019

基金项目:

江苏省科技厅科技项目面上项目 BK20181424

南京同仁堂经典名方产品研发项目 2018053

南京同仁堂经典名方产品研发项目 2018054

详细信息

作者简介:
李华露, 女, 硕士研究生, E-mail: 1941062535@qq.com

通讯作者:
程建明, 男, 研究员, 主要从事中药新剂型新技术及产品开发研究，E-mail: cjm7895@163.com

中图分类号: R284
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- 被引次数: 0
出版历程
- 收稿日期: 2022-01-27
- 网络出版日期: 2022-07-09
- 发布日期: 2022-07-10

Establishment of HPLC Characteristic Chromatogram and Study on Quality Value Transmitting of Substance Benchmarks of Yihuang Decoction

LI Hua-lu^{1, 2
,},
LI Qiu-tong^{1, 2},
LIU Hua-lan^{1, 2},
LIU Tao-shi^{1, 2},
JI Jing^{1, 2},
CHENG Jian-ming^{1, 2
, ,},
GUO Qing³

1.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
2.
Jiangsu Province Engineering Research Center of Classical Prescription, Nanjing 210023, China
3.
Jiangsu Institute of Food and Drug Control, Nanjing 210019, China

摘要

摘要: 目的建立易黄汤物质基准的HPLC特征图谱和易黄汤中指标性成分尿囊素、没食子酸、京尼平苷酸和小檗碱的含量测定方法, 阐明这4种成分在饮片-水煎液-物质基准的量值传递规律。方法采用Agilent ZORBAX SB-Aq色谱柱(250 mm×4.6 mm, 5 μm), 以乙腈-0.1%乙酸水溶液为流动相, 梯度洗脱, 采用多波长切换法, 检测波长分别为205、254、280 nm, 以上述4种成分的转移率为主要评价指标, 研究从饮片-水煎液-物质基准的量值传递规律。结果建立了易黄汤物质基准的HPLC特征图谱, 15批物质基准冻干粉样品相似度均大于0.90, 共标定出15个共有峰, 指认出其中5个特征峰(2号峰尿囊素、4号峰没食子酸、6号峰京尼平苷酸、7号峰黄柏碱、15号峰小檗碱); 同时进行含量测定, 15批物质基准中尿囊素、没食子酸、京尼平苷酸、小檗碱的含量范围分别为0.801%~1.087%、0.047%~0.057%、0.037%~0.081%、0.250%~0.387%;15批易黄汤水煎液到物质基准的量值传递(转移率)分别为尿囊素73.09%~91.37%、没食子酸74.99%~89.32%、京尼平苷酸71.77%~94.38%、小檗碱76.54%~88.43%。结论建立的特征图谱和4种成分的含量测定方法能较好地控制易黄汤物质基准的质量, 量值传递结果表明物质基准冻干粉的制备工艺具有科学性和稳定性, 为经典名方易黄汤制剂的后续开发打下了基础。
- 经典名方 /
- 易黄汤 /
- 物质基准 /
- 特征图谱 /
- 量值传递
Abstract: OBJECTIVE To establish the HPLC characteristic chromatogram, simultaneously determinate the contents of allantoin, gallic acid, geniposidic acid and berberine in the substance benchmark of Yihuang Decoction, and clarify the quality value transmitting rules from decoction pieces to water decoction to substance benchmarks. METHODS Agilent ZORBAX SB-Aq chromatographic column (250 mm×4.6 mm, 5 μm) was used, eluted with acetonitrile-0.1% acetic acid in gradient elution, and the detection wavelength was 205, 254, and 280 nm, respectively. The transfer rates of the above four components were used as the indexes for quality evaluation to study the quality value transmitting rule from decoction pieces to water decoction to substance benchmarks. RESULTS The HPLC characteristic chromatogram of Yihuang Decoction was established, the similarity of 15 batches of samples was greater than 0.90, and a total of 15 common peaks were found and five of them [allantoin (peak 2), gallic acid (peak 4), geniposidic acid (peak 6), phellodendrine (peak 7), berberine (peak 15)] were identified. The contents of allantoin, gallic acid, geniposidic acid and berberine in 15 batches of benchmarks were 0.801%-1.087%, 0.047%-0.057%, 0.037%-0.081%, 0.250%-0.387%, respectively. The transfer rates (from water decoction to substance benchmarks) of allantoin, gallic acid, geniposidic acid and berberine were 73.09%-91.37%, 74.99%-89.32%, 71.77%-94.38%, 76.54%-88.43%, respectively. CONCLUSION The HPLC characteristic chromatogram combined with the analytical method of multicomponents in simultaneous quantitation established in this experiment are stable and reliable, which can provide a theoretical guidance for the quality evaluation of Yihuang Decoction. The quality value transmitting results shows that the preparing technology of substance benchmarks is scientific and stable, which can lay a foundation for the subsequent development of classic prescription Yihuang Decoction preparation.
- classical prescriptions /
- Yihuang Decoction /
- substance benchmarks /
- characteristic chromatogram /
- quality value transmitting

HTML全文

图 1 混合对照品HPLC图(A)及15批易黄汤物质基准HPLC特征图谱(B)

注: 2.尿囊素; 4.没食子酸; 6.京尼平苷酸; 7.黄柏碱; 15.小檗碱

Figure 1. HPLC of mixed control solution (A) and characteristic chromatogram of 15 batches of Yihuang Decoction substance benchmark (B)

下载: 全尺寸图片幻灯片

图 2 易黄汤专属性考察HPLC图

注：A.炒山药单味样品; B.炒芡实单味样品; C.炒白果单味样品; D.酒车前子单味样品; E.盐黄柏单味样品; F.缺炒山药阴性样品; G.缺炒芡实阴性样品; H.缺炒白果阴性样品; I.缺酒车前子阴性样品; J.缺盐黄柏阴性样品; K.易黄汤全方样品

Figure 2. HPLC chromatogram of Yihuang Decoction for specific investigation

下载: 全尺寸图片幻灯片

图 3 易黄汤物质基准中4种成分HPLC图

注：A.混合对照品; B.205 nm; C.254 nm; D.280 nm; 2.尿囊素; 4.没食子酸; 6.京尼平苷酸; 15.小檗碱

Figure 3. HPLC chromatograms of four ingredients of Yihuang Decoction substance benchmark

下载: 全尺寸图片幻灯片

表 1 易黄汤饮片来源

Table 1. Sources of Yihuang Decoction pieces

名称	炮制工艺	批号	产地
炒山药	取净山药片, 置热锅中, 140 ℃炒制约60 min, 炒至表面微黄色, 取出, 晾凉。	2021110401~2021110404 2021110501~2021110506	河南温县河南武陟
炒芡实	取净芡实, 置热锅中, 160 ℃炒制约70 min, 炒至表面微黄色, 取出, 晾凉。	2021083101~2021083106 2021091101~2021091104	江苏高邮
炒白果	取净白果仁, 置热锅中, 180 ℃炒制约15 min, 炒至表面色泽加深, 略有焦斑, 横断面胶质样, 外层黄色, 内层淡黄色, 粉性, 中间有空隙。有香气。	2021081001~2021081010	江苏邳州
酒车前子	取净车前子, 喷淋定量黄酒拌匀, 闷润0.5 h, 待酒被吸尽后, 180 ℃炒至爆裂声起, 略有香气逸出时, 取出晾凉。每100 kg车前子, 用黄酒20 kg。	2021063001~2021063004 2021070101~2021070106	江西新干
盐黄柏	取原药材, 除去杂质, 洗净, 加水喷淋(水量为药材质量的15%), 闷润约45 min至内外湿度一致, 切丝(1 cm), 70 ℃烘30 min, 至干。取净黄柏丝, 加30%药材量的水配制食盐水, 闷润约0.5 h, 待盐水被吸尽后, 置热锅中, 160 ℃炒制约40 min, 至干。每100 kg黄柏, 用食盐2 kg。	2021073101~2021073105 2021080101~2021080105	四川大邑四川雅安

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表 2 易黄汤15批物质基准对应的饮片批次

Table 2. 15 batches of Yihuang Decoction substance benchmark corresponding to the batches of decoction pieces

批号	炒山药	炒芡实	炒白果	盐黄柏	酒车前子
S1	2021110402	2021083105	2021081001	2021073103	2021070101
S2	2021110501	2021083103	2021081004	2021073104	2021063001
S3	2021110403	2021083104	2021081009	2021073105	2021063004
S4	2021110502	2021091104	2021081006	2021080101	2021063002
S5	2021110404	2021091103	2021081004	2021080102	2021063003
S6	2021110503	2021091101	2021081005	2021073103	2021063001
S7	2021110403	2021091102	2021081008	2021073104	2021063004
S8	2021110501	2021083103	2021081007	2021073102	2021070106
S9	2021110502	2021083101	2021081002	2021073103	2021070105
S10	2021110401	2021083106	2021081005	2021073101	2021070103
S11	2021110506	2021083101	2021081004	2021073104	2021070102
S12	2021110402	2021083104	2021081010	2021080104	2021070104
S13	2021110504	2021091103	2021081009	2021080105	2021070102
S14	2021110505	2021083103	2021081002	2021080103	2021070105
S15	2021110502	2021083102	2021081003	2021073102	2021070106

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表 3 易黄汤15批物质基准特征图谱的相似度

Table 3. The similarity of 15 batches of Yihuang Decoction substance benchmark

	S1	S2	S3	S4	S5	S6	S7	S8	S9	S10	S11	S12	S13	S14	S15	对照
S1	1	0.984	0.985	0.985	0.985	0.985	0.985	0.985	0.984	0.985	0.986	0.986	0.984	1	1	0.985
S2		1	0.999	0.999	0.996	0.996	0.996	0.968	0.968	0.966	0.999	0.999	1	0.984	0.985	0.986
S3			1	1	0.995	0.995	0.995	0.967	0.967	0.967	1	1	0.999	0.985	0.985	0.975
S4				1	0.995	0.995	0.995	0.967	0.967	0.967	1	1	0.999	0.985	0.985	0.964
S5					1	1	1	0.972	0.972	0.971	0.995	0.995	0.997	0.985	0.985	0.997
S6						1	1	0.972	0.972	0.97	0.996	0.996	0.997	0.985	0.985	0.989
S7							1	0.972	0.972	0.971	0.995	0.995	0.996	0.985	0.985	0.998
S8								1	0.999	0.999	0.968	0.968	0.968	0.983	0.984	0.977
S9									1	0.999	0.968	0.968	0.968	0.983	0.984	0.986
S10										1	0.968	0.968	0.967	0.984	0.984	0.988
S11											1	1	0.999	0.985	0.986	0.985
S12												1	0.999	0.986	0.986	0.997
S13													1	0.984	0.984	0.99
S14														1	1	0.968
S15															1	0.998

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表 4 含量测定方法学考察结果(%，n=6)

Table 4. Assay methodology (%, n=6)

指标性成分	回归方程	R²	RSD			平均加样回收率
指标性成分	回归方程	R²	精密度	重复性	稳定性	平均加样回收率
尿囊素	y=22 793x+164 611	0.999 1	1.4	0.9	0.9	108.23
没食子酸	y=59 952x-139 067	0.999 8	1.0	1.2	1.5	104.60
京尼平苷酸	y=13 829x-15 788	0.999 9	0.6	0.7	0.7	103.08
小檗碱	y=60 255x-49 006	0.999 9	0.3	0.9	0.7	99.69
注: 专属性均良好。

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表 5 饮片中指标性成分的含量(%, n=2)

Table 5. Content of index components in decoction pieces (%, n=2)

批次	尿囊素	没食子酸	京尼平苷酸	小檗碱
S1	0.631	0.033	1.333	4.928
S2	0.621	0.034	1.226	5.439
S3	0.543	0.031	1.273	4.952
S4	0.558	0.028	1.271	4.883
S5	0.574	0.029	1.225	4.900
S6	0.495	0.034	1.226	4.928
S7	0.543	0.027	1.273	5.439
S8	0.621	0.034	1.273	5.022
S9	0.548	0.034	1.327	4.928
S10	0.463	0.033	1.099	5.434
S11	0.462	0.034	1.100	4.928
S12	0.495	0.031	1.321	5.320
S13	0.574	0.029	1.100	4.919
S14	0.621	0.034	1.327	5.405
S15	0.548	0.026	1.273	5.029
x±s	0.553±0.056	0.031±0.003	1.243±0.082	5.097±0.232

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表 6 水煎液中指标性成分的含量及出膏率(%, n=2)

Table 6. Content of index components and extraction rate in Decoction (%, n=2)

批次	水煎液中含量				出膏率
批次	尿囊素	没食子酸	京尼平苷酸	小檗碱	出膏率
S1	0.187 7	0.008 0	0.012 8	0.054 2	13.94
S2	0.181 2	0.008 0	0.012 9	0.054 4	14.64
S3	0.173 5	0.007 8	0.012 1	0.052 8	14.70
S4	0.156 2	0.009 1	0.007 1	0.045 2	14.33
S5	0.160 6	0.009 1	0.005 6	0.040 1	15.14
S6	0.151 7	0.009 1	0.005 5	0.040 2	14.04
S7	0.168 8	0.008 4	0.008 9	0.054 9	13.19
S8	0.170 0	0.008 4	0.009 1	0.054 8	12.49
S9	0.177 4	0.008 4	0.009 2	0.054 8	12.84
S10	0.158 4	0.008 0	0.010 8	0.056 7	14.90
S11	0.158 7	0.008 0	0.011 0	0.056 8	16.37
S12	0.157 0	0.008 0	0.010 9	0.056 7	15.16
S13	0.143 3	0.007 8	0.010 7	0.064 1	16.29
S14	0.150 8	0.007 8	0.010 8	0.064 0	15.63
S15	0.145 2	0.007 8	0.010 8	0.064 2	14.77
x±s	0.163±0.013	0.008±0.001	0.010±0.002	0.054±0.008	14.560±1.138

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表 7 物质基准中指标性成分的含量及干粉得率(%, n=2)

Table 7. Content of index components and dry powder yield in substance standard (%, n=2)

批次	物质基准中含量				干粉得率
批次	尿囊素	没食子酸	京尼平苷酸	小檗碱	干粉得率
S1	1.087	0.049	0.080	0.338	12.89
S2	1.072	0.050	0.081	0.339	13.20
S3	1.079	0.050	0.081	0.339	13.07
S4	0.958	0.057	0.037	0.250	13.79
S5	0.999	0.057	0.037	0.250	13.44
S6	1.003	0.057	0.038	0.254	13.30
S7	1.068	0.051	0.057	0.353	12.36
S8	1.058	0.052	0.058	0.355	12.30
S9	1.054	0.051	0.058	0.352	12.42
S10	1.001	0.052	0.075	0.365	13.66
S11	0.944	0.052	0.075	0.366	13.54
S12	0.992	0.052	0.076	0.367	13.50
S13	0.865	0.047	0.066	0.383	14.61
S14	0.850	0.048	0.067	0.387	14.62
S15	0.801	0.047	0.066	0.384	14.66
x±s	0.989±0.090	0.051±0.003	0.063±0.016	0.339±0.048	13.420±0.777

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表 8 饮片到水煎液中指标性成分的转移率(%, n=2)

Table 8. Transfer rate of index components from decoction pieces to Decoction (%, n=2)

批次	尿囊素	没食子酸	京尼平苷酸	小檗碱
S1	76.37	61.26	24.75	14.13
S2	74.89	60.73	26.98	12.84
S3	82.04	65.05	24.34	13.68
S4	71.82	84.16	14.27	11.88
S5	71.87	81.05	11.73	10.50
S6	78.69	69.02	11.54	10.46
S7	79.85	80.97	18.00	12.96
S8	70.25	63.93	18.27	14.01
S9	83.05	63.68	17.79	14.27
S10	87.76	63.03	25.15	13.39
S11	88.17	61.20	25.60	14.81
S12	81.48	67.32	21.22	13.70
S13	64.16	69.52	24.96	16.73
S14	62.34	59.73	20.85	15.20
S15	67.99	78.14	21.74	16.39
x±s	76.05±7.95	68.59±8.38	20.48±5.06	13.66±1.81

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表 9 水煎液到物质基准中指标性成分的转移率及浸膏转移率(%, n=2)

Table 9. Transfer rate of index components and extract from Decoction to substance standard (%, n=2)

批次	水煎液到物质基准指标成分转移率				浸膏转移率
批次	尿囊素	没食子酸	京尼平苷酸	小檗碱	浸膏转移率
S1	74.61	79.27	80.71	80.40	92.44
S2	76.28	81.15	81.16	80.27	90.15
S3	80.16	83.60	86.12	82.74	88.88
S4	84.69	87.05	71.77	76.54	96.24
S5	85.90	86.37	90.52	86.29	88.81
S6	91.37	87.46	94.38	87.41	94.72
S7	77.79	74.99	78.82	78.99	93.71
S8	76.54	75.57	78.75	79.62	98.52
S9	73.09	75.28	77.36	79.11	96.75
S10	85.59	88.30	93.97	87.06	91.65
S11	80.52	88.42	92.68	87.12	82.71
S12	85.51	88.12	93.82	87.67	89.05
S13	88.20	89.27	90.96	87.27	89.72
S14	82.44	89.32	90.43	88.43	93.53
S15	80.72	88.24	89.06	87.51	99.24
x±s	81.56±5.30	84.16±5.44	86.03±7.30	83.76±4.17	92.41±4.39

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