collaboration for herbal medicines between nifds & usp · 2019-07-22 · hptlc with osthole,...
TRANSCRIPT
Collaboration for Herbal Medicinesbetween NIFDS & USP
Ph.D. Jonghwan Kim
Herbal Medicine Research DivisionNational Institute of Food and Drug Safety Evaluation
Ministry of Food and Drug Safety
I. Progress since MOU
II. Current status
III. Move forward
Contents
I. Progress since MOU
MOU signed (’12.7)
Works based on chemical medicine (’15~)
Extensive works including biologicals and herbal medicine (’15.6)
Agreed USP executive exchange program for herbal medicine (’16.6)
NIFDS expert(Dr. Jonghwan Kim) visited DSHM USPC (’17.2~’18.7)
Developed monograph draft for 6 items including
Angelica gigas root etc
USPC expert(Dr. Nam-Cheol Kim) visited NIFDS (‘18.10)
Progress since MOU
II. Current Status
- Organize working group & consensus item
- Co-develop monograph
(1) Organize small working group (1st Apr 29, 2nd May 30)
To discuss the analytical data during the development of
monographs
To monitor the progress of collaboration in fields of
herbal medicines; and/or
help the outcome of collaboration be productive
Working group
Angelica gigas (당귀)
Forsythia suspensa (연교)
Foeniculum vulgare (회향)
Perilla frutescens, P. frutescens var. crispa (자소엽)
Magnolia obovata (후박)
Epimedium koreanum (음양곽)
(2) 6 items in-progress
Consensus item
Ongoing Items (당귀)
Ongoing Items (연교)
Current monograph in KP & HMC
Co-development process- Angelica gigas root
KP11 HMC (development stage)
Origin Angelica gigas (Umbelliferae) / Root
Description Macroscopic, Microscopic
Identification TLC with Korean RMPM
a. HPTLC with osthole, imperatorin, isoimperatorin
SST validation: To Comeb. HPLC with four CRS
Content(as dried basis)
nodakenin, decursin, decursinolangelate 6.0 % (HPLC)
chlorogenic acid, demethylsuberosin, decursin, decursinol angelate 4.2 % (HPLC)
Loss on Drying - To Come <731>
Total Ash 6.0 %
Acid Insoluble Ash - To Come <561>
Extractives -Alcohol-Soluble (Method 1): To ComeWater-Soluble (Method 2): To Come
KP11 HMC (development stage)
Foreign matter 5.0 % / 1.0 % -
Heavy metal As 3.0, Cd 0.3, Pb 5.0, Hg 0.2 ug/g
Pesticide 14 (Total DDT etc) 70 (Total DDT etc)
Microbial Enumeration test
-Total aerobic bacteria 105 cfu/g
Total combined molds, yeasts 103 cfu/gGram (-) bacteria 103 cfu/g
Specified microorganism
- Salmonella, E. coli absence
Sulfur dioxide 30 ppm -
Aflatoxin -AFb1 5 ppb
Total AF(b1, b2, g1, g2) 20 ppb
Current monograph in KP & HMC
Co-development process- Angelica gigas root
Microscopic Identification (transverse section, x200)
a. vessel, b. cork cell, c. secretory canal, d. starch
e. bast fiber bundles, f. scalariform vessel, g. spiral vessel, h. starch
AG4 AG13 AG20
Co-development process- Angelica gigas root
n=20 min ~ Max (%) Average ± SD (%) % RSD
Loss on Drying 9.2 ~ 11.8 10.0 ± 0.8 8.3
Total Ash 4.6 ~ 6.2 5.5 ± 0.4 6.5
Acid-Insoluble Ash 0.8 ~ 1.1 0.9 ± 0.1 12.3
Extractives(diluted ethanol)
53.8 ~ 57.9 55.0 ± 1.3 2.4
Co-development process- Angelica gigas root
n=20 min ~ Max (%) Average ± SD (%) % RSD
Content 4.6 ~ 9.1 6.6 ± 1.3 20.3
y = 166161x - 48101
R² = 0.9998
0
1,000,000
2,000,000
3,000,000
4,000,000
5,000,000
6,000,000
7,000,000
0 10 20 30 40 50
y = 288678x + 30144
R² = 1
0
1,000,000
2,000,000
3,000,000
4,000,000
5,000,000
6,000,000
7,000,000
0 5 10 15 20 25
y = 252030x + 205128
R² = 1
0
10,000,000
20,000,000
30,000,000
40,000,000
50,000,000
60,000,000
0 50 100 150 200 250
y = 259942x - 77934
R² = 0.9997
0
10,000,000
20,000,000
30,000,000
40,000,000
50,000,000
60,000,000
70,000,000
0 50 100 150 200 250 300
Co-development process- Angelica gigas root
KP11 HMC (development stage)
Origin F. suspensa, F. viridissima F. suspensa
Description Macroscopic, Microscopic
Identification Derivatization
a. HPTLC with forsythoside a, lariciresinol, forsythin, pinoresinol, phillygenin
SST validation: To Comeb. HPLC with five CRS
Content(as dried basis)
F. suspensa: forsythoside a 0.25 %F. viridissima: arctigenin 0.4 % (HPLC)
forsythoside a, lariciresinol, forsythin, pinoresinol, phillygenin 2.4 % (HPLC)
Loss on Drying - To Come <731>
Total Ash 5.0 %
Acid Insoluble Ash - To Come <561>
Extractives diluted ethanol 10.0 %Alcohol-Soluble (Method 1): To ComeWater-Soluble (Method 2): To Come
Current monograph in KP & HMC
Co-development process- Forsythia suspensa fruit
KP11 HMC (development stage)
Foreign matter 5.0 % 2.0 %
Heavy metal As 3.0, Cd 0.3, Pb 5.0, Hg 0.2 ug/g
Pesticide 5 (Total DDT etc) 70 (Total DDT etc)
Microbial Enumeration test
-Total aerobic bacteria 105 cfu/g
Total combined molds, yeasts 103 cfu/gGram (-) bacteria 103 cfu/g
Specified microorganism
- Salmonella, E. coli absence
Sulfur dioxide 30 ppm -
Aflatoxin -AFb1 5 ppb
Total AF(b1, b2, g1, g2) 20 ppb
Co-development process- Forsythia suspensa fruit
Current monograph in KP & HMC
Microscopic Identification (transverse section, x200)
a. epicarp, b. vascular bundle, c. stone cell, d. endocarp
FS4 FS8 FS16
Co-development process- Forsythia suspensa fruit
n=21 min ~ Max (%) Average ± SD (%) % RSD
Loss on Drying 7.8 ~ 10.5 8.9 ± 0.7 7.6
Total Ash 2.1 ~ 3.5 3.0 ± 0.3 9.2
Acid-Insoluble Ash 0.2 ~ 0.6 0.3 ± 0.1 30.0
Extractives (diluted ethanol)
25.0 ~ 41.5 33.7 ± 7.1 21.2
Co-development process- Forsythia suspensa fruit
n=21 min ~ Max (%) Average ± SD (%) % RSD
Content 0.3 ~ 12.0 8.0 ± 3.3 42.0
y = 8.5403x + 39.237
R² = 1
0.00000
5,000.00000
10,000.00000
15,000.00000
0 500 1,000 1,500 2,000
y = 8.6906x + 2.982
R² = 0.9999
0.00000
200.00000
400.00000
600.00000
0 20 40 60 80
y = 4.8447x + 1.801
R² = 0.9999
0.00000
100.00000
200.00000
300.00000
400.00000
0 10 20 30 40 50 60 70
y = 8.3984x + 0.8532
R² = 0.9999
0.00000
50.00000
100.00000
150.00000
200.00000
0 5 10 15 20 25
y = 8.9763x + 6.0376
R² = 0.9997
0.00000
50.00000
100.00000
150.00000
200.00000
0 5 10 15 20 25
forsythoside a lariciresinol forsythin
pinoresinol
phillygenin
Co-development process- Forsythia suspensa fruit
III. Move forward
Gap review & Harmonization
KP/KHP USP (GC 561)
Heavy metalindividual elements (Pb, As, Cd, Hg)comprehensive application based on risk assessment
Pesticidedifferent kind of pesticides and/or different specificationscomprehensive application based on risk assessment
Sulfur dioxide comprehensive application no regulation
Benzopyrenea few botanicals with detection record & risk assessment
no regulation
Microorganism no regulation comprehensive application
Aflatoxina few botanicals with detection record & risk assessment
a few botanicals
Differences in Specification
KP/KHP USP (GC 561)
Total Ash2~4 g
500~550 ℃ for 4h2~4 g
675 ± 25 ℃
Acid Insoluble
Ash
2~4 g10 % hydrochloric acid
25 mL for 5 min
2~4 g3 N hydrochloric acid
25 mL for 5 min(3 N ≒ 9.99 % with commercial
conc. 37 % HCl)
Differences in Test Method
Gap review & Harmonization
KP/KHP USP (GC 561)
AlcoholSoluble
(M1, hot ext)-
4 gEthyl alcohol 100 mL for 1h
Reflux extraction for 1hTransfer 25mL, Dry 105℃ for
6h
AlcoholSoluble
(M2, cold ext)
2.3 g50 % Ethyl alcohol 70 mL
Shake for first 5h, then stand 24hr
Transfer 50 mL, Dry 105℃ for 4h
4 gEthyl alcohol 100 mL for 24h
Shake for first 8hTransfer 25 mL, Dry 105℃
Differences in Test Method
Gap review & Harmonization
Thank you for your attention!