ISO/FDIS 23962

Traditional Chinese Medicine -- Processed Aconitum carmichaelii lateral root

Médecine traditionnelle chinoise -- Racine latérale d'aconit de Carmichael (Aconitum carmichaelii) transformée

General Information

• Status: Published
• ICS: 11.120.10 - Medicaments
• Technical Committee: ISO/TC 249 - Traditional Chinese medicine
• Drafting Committee: ISO/TC 249/WG 1 - Quality and safety of raw materials and traditional processing
• Current Stage: 5020 - FDIS ballot initiated: 2 months. Proof sent to secretariat
• Start Date: 26-Apr-2021
• Completion Date: 26-Apr-2021

Standards Content (sample)

FINAL
INTERNATIONAL ISO/FDIS
DRAFT
STANDARD 23962
ISO/TC 249
Traditional Chinese Medicine —
Secretariat: SAC
Processed Aconitum carmichaelii
Voting begins on:
2021­04­26 lateral root
Voting terminates on:
2021­06­21
RECIPIENTS OF THIS DRAFT ARE INVITED TO
SUBMIT, WITH THEIR COMMENTS, NOTIFICATION
OF ANY RELEVANT PATENT RIGHTS OF WHICH
THEY ARE AWARE AND TO PROVIDE SUPPOR TING
DOCUMENTATION.
IN ADDITION TO THEIR EVALUATION AS
Reference number
BEING ACCEPTABLE FOR INDUSTRIAL, TECHNO­
ISO/FDIS 23962:2021(E)
LOGICAL, COMMERCIAL AND USER PURPOSES,
DRAFT INTERNATIONAL STANDARDS MAY ON
OCCASION HAVE TO BE CONSIDERED IN THE
LIGHT OF THEIR POTENTIAL TO BECOME STAN­
DARDS TO WHICH REFERENCE MAY BE MADE IN
NATIONAL REGULATIONS. ISO 2021
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ISO/FDIS 23962:2021(E)
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© ISO 2021

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ii © ISO 2021 – All rights reserved
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ISO/FDIS 23962:2021(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Descriptions .............................................................................................................................................................................................................. 2

5 Requirements .......................................................................................................................................................................................................... 3

5.1 Morphological features of root .................................................................................................................................................. 3

5.1.1 Salted Aconitum carmichaelii lateral root .............................................................................................. 3

5.1.2 Black slice of Aconitum carmichaelii lateral root ............................................................................. 3

5.1.3 White slice of Aconitum carmichaelii lateral root............................................................................ 4

5.1.4 Boiled slice of Aconitum carmichaelii lateral root........................................................................... 4

5.2 Moisture ........................................................................................................................................................................................................ 4

5.3 Total ash ........................................................................................................................................................................................................ 4

5.4 Thin-layer chromatogram (TLC) identification .......................................................................................................... 4

5.5 Marker compounds ............................................................................................................................................................................. 4

5.6 Heavy metals ............................................................................................................................................................................................. 4

5.7 Pesticide residues ................................................................................................................................................................................. 5

6 Sampling ........................................................................................................................................................................................................................ 5

7 Test methods ............................................................................................................................................................................................................. 5

7.1 Macroscopic identification ........................................................................................................................................................... 5

7.2 Determination of moisture content ...................................................................................................................................... 6

7.3 Determination of total ash content........................................................................................................................................ 6

7.4 Thin-layer chromatogram (TLC) identification .......................................................................................................... 6

7.5 Determination of marker compounds ................................................................................................................................ 6

7.6 Determination of heavy metal content............................................................................................................................... 6

7.7 Determination of pesticide residue content .................................................................................................................. 6

7.8 Roots number/1000 g ...................................................................................................................................................................... 6

8 Test report ................................................................................................................................................................................................................... 6

9 Packaging, storage and transportation ......................................................................................................................................... 6

10 Marking and labelling ..................................................................................................................................................................................... 7

Annex A (informative) Determination of moisture content ......................................................................................................... 8

Annex B (informative) Thin-layer chromatogram (TLC) identification ........................................................................... 9

Annex C (informative) Reference information of national and regional requirements for

processed Aconitum carmichaelii lateral root ....................................................................................................................11

Annex D (informative) Reference information of commercial grading requirements for

Aconitum carmichaelii lateral root .................................................................................................................................................15

Bibliography .............................................................................................................................................................................................................................16

© ISO 2021 – All rights reserved iii
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ISO/FDIS 23962:2021(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non­governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/ patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and

expressions related to conformity assessment, as well as information about ISO's adherence to the

World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www .iso .org/

iso/ foreword .html.

This document was prepared by Technical Committee ISO/TC 249, Traditional Chinese medicine.

Any feedback or questions on this document should be directed to the user’s national standards body. A

complete listing of these bodies can be found at www .iso .org/ members .html.
iv © ISO 2021 – All rights reserved
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ISO/FDIS 23962:2021(E)
Introduction

Processed Aconitum carmichaelii lateral root (Aconiti Lateralis Radix, Fuzi, 附子) has been used as a

herbal medicine in traditional Chinese medicine for a very long time. It remains a highly valued herb

today because of its significant effects. Aconitum carmichaelii lateral root is one of the most frequently

used herbal medicines in traditional Chinese medicine. Of an approximate total of 80 0000 traditional

Chinese medicine formulas, around 7,04 % of formulations include Aconitum carmichaelii lateral root

[1]

as an ingredient. Among 113 formulas in the Treatise on Cold Pathogenic Diseases (伤寒论), one of four

great classics of traditional Chinese medicine, there are 23 formulations with Aconitum carmichaelii

lateral root (occupying 20,35 %) as an ingredient. Among 202 formulas in the Synopsis of Golden

[2]

Chamber (金匮要略), another of the four great classics of traditional Chinese medicine, there are 26

prescriptions with Aconitum carmichaelii lateral root as an ingredient (12,87 %). Among 148 Kampo

medicines for prescription from the Ministry of Health, Labour and Welfare (MHLW) of Japan, there are

10 prescriptions with Aconitum carmichaelii lateral root as an ingredient (6,76 %).

Processed Aconitum carmichaelii lateral root contains aconitum alkaloids which have anti-inflammatory,

analgesic and cardiotonic activities. These aconitum alkaloids are irreplaceably effective for injuries,

arthritis, neuropathic pain, sequelae of apoplexy, stomach pain, stomach crymodynia, menoxenia,

abscesses, deep­rooted carbuncles and sores. Aconitum alkaloids are, however, a double­edged sword.

At present, international trade in processed Aconitum carmichaelii lateral root is restricted in a number

of nations due to the high natural toxicity of processed Aconitum carmichaelii lateral root. Also, there

are sporadic cases of aconitum alkaloid poisoning reported worldwide due to misuse.

Nonetheless, the toxicity of processed Aconitum carmichaelii lateral root can be reduced dramatically

with proper processing (such as repeated boiling or steaming), prolonged decocting and dose control.

However, standards for processed Aconitum carmichaelii lateral root are not yet harmonized at an

international level and regulatory authorities in many nations do not adequately differentiate highly

toxic forms from less-toxic forms (or even non-toxic forms) of Aconitum carmichaelii lateral root.

The six aconite alkaloids [Aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine

(BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA)] are commonly used as chemical

[3]

markers for quality control of processed Aconitum carmichaelii lateral root. AC, MA and HA are toxic

diester diterpenoid alkaloids, while BAC, BMA and BHA are active monoester diterpenoid alkaloids.

To guarantee safety, efficacy and quality, these six alkaloids are commonly controlled in different

pharmacopoeia. Nevertheless, poisoning cases are still occasionally reported. From 1989 to 2010, 140

[4]

cases of aconitum poisoning, including one fatal case, were reported in Hong Kong. Additionally,

17 cases were reported in Taiwan from 1990 to 1999, 2017 cases were reported in China from 1989

[5]

to 2008 and 121 cases were reported in Korea from 1995 to 2007. Multiple reasons for aconitum

poisoning exist, include overdoses, inadequate processing, aconitum contamination in other herbs,

dispensing and management errors, and hidden risk factors. In the 17 cases reported in Hong Kong,

yunaconitine (YAC), crassicauline A (CCA) and 8-deacetyl-yunaconitine (DYA) were detected instead

[4,6]

of AC, MA and HA in the urine samples of the aconitum poisoning patients. Because YAC, DYA and

CCA were detected in the urine of the aconitum poisoning patients, these alkaloids are considered to be

[6]

hidden risk factors and should be covered in laboratory screenings for toxic compounds. Therefore,

an International Standard is required for Aconitum carmichaelii lateral root for quality control of the

[5]
herb and its products and to ensure the safe use of these medical materials .

This document provides a systematic and practical International Standard for Aconitum carmichaelii

lateral root to control and guarantee stable quality, to ensure safe and effective use in clinics, to

standardize the global market trade and to reduce cases of aconite poisoning.

As national implementation can differ, national standards bodies are invited to modify the values given

in 5.2, 5.3 and 5.5 in their national standards. Examples of national and regional values are given in

Annex C.
© ISO 2021 – All rights reserved v
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FINAL DRAFT INTERNATIONAL STANDARD ISO/FDIS 23962:2021(E)
Traditional Chinese Medicine — Processed Aconitum
carmichaelii lateral root
1 Scope

This document specifies minimum requirements and test methods for processed Aconitum carmichaelii

lateral root (lateral root of Aconitum carmichaelii Debx.).

This document applies to processed Aconitum carmichaelii lateral root that is sold and used as natural

medicines in international trade, including Chinese materia medica (whole medicinal materials) and

decoction pieces derived from this plant. Processing methods of Aconitum carmichaelii lateral root are

excluded.
2 Normative references

The following documents are referred to in the text in such a way that some or all of their content

constitutes requirements of this document. For dated references, only the edition cited applies. For

undated references, the latest edition of the referenced document (including any amendments) applies.

ISO 1575, Tea — Determination of total ash

ISO 18664, Traditional Chinese Medicine — Determination of heavy metals in herbal medicines used in

Traditional Chinese Medicine

ISO 21371, Traditional Chinese medicine — Labelling requirements of products intended for oral or topical use

ISO 22217, Traditional Chinese medicine —Storage requirements for raw materials and decoction pieces

ISO 22258, Traditional Chinese medicine — Determination of pesticide residues in natural products by gas

chromatography

ISO 23191, Traditional Chinese medicine — Determination of selected Aconitum alkaloids by high-

performance liquid chromatography (HPLC)
World Health Organization Quality control methods for herbal materials, 2011
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
fresh Aconitum carmichaelii lateral root

fresh lateral root of Aconitum carmichaelii Debx. with the tap root, rootlet and soil removed

3.2
Aconitum carmichaelii lateral root
unprocessed dried lateral root of Aconitum carmichaelii Debx.
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ISO/FDIS 23962:2021(E)
3.3
processed Aconitum carmichaelii lateral root
dried lateral root of Aconitum carmichaelii Debx. after processing

Note 1 to entry: This includes commercial varieties such as salted Aconitum carmichaelii lateral root, black slice

of Aconitum carmichaelii lateral root and white slice of Aconitum carmichaelii lateral root.

3.4
salted Aconitum carmichaelii lateral root
processed Aconitum carmichaelii lateral root in bittern

Note 1 to entry: The decoction pieces are processed with the following method: select the large and uniform

fresh Aconitum carmichaelii lateral root; wash clean and soak overnight in bittern, of which the main ingredient is

edible calcium chloride solution; add salt, soak and take out to sun-dry and air-dry every day; gradually prolong

the drying time until a lot of salt is crystallized on the surface of the drug and its texture becomes hard.

Note 2 to entry: Bittern is liquid residue of mineral salt, the major constituent being magnesium chloride.

3.5
black slice of Aconitum carmichaelii lateral root
processed Aconitum carmichaelii lateral root in bittern with dye

Note 1 to entry: The decoction pieces are processed with the following method: select the large and uniform

fresh Aconitum carmichaelii lateral root; wash clean and soak in bittern for several days; boil in the infusion

thoroughly; take out, rinse in water, cut longitudinally into slices about 0,5 cm in thickness; soak and rinse in

water once again; stain the slices dark brown (e.g. with black bean decoction, strong tea water) and steam them

until they turn oily and lustrous; bake the slices to half-dryness, then sun-dry or bake to complete dryness.

3.6
white slice of Aconitum carmichaelii lateral root
processed Aconitum carmichaelii lateral root in bittern without bark

Note 1 to entry: The decoction pieces are processed with the following method: select the large and uniform

fresh Aconitum carmichaelii lateral root; wash clean and soak in bittern for several days; boil in the infusion

thoroughly; take out, peel the bark and cut longitudinally into slices about 0,3 cm in thickness; soak and rinse in

water, take out, steam thoroughly, sun-dry to dryness.
3.7
boiled slice of Aconitum carmichaelii lateral root

processed Aconitum carmichaelii lateral root with salt, Glycyrrhizae root and black beans

Note 1 to entry: The decoction pieces are processed with the following method: blanch salted Aconitum

carmichaelii lateral root with water two or three times a day until all the salt is rinsed out; boil together with

Glycyrrhizae root, black beans and water until the centre of the cut surface is devoid of white core and the cut

slice is numb to the tongue; remove Glycyrrhizae root and black beans, cut the drug into slices and dry.

3.8
batch

samples collected from the same particular place at the same time, of no more than 5 000 kg

4 Descriptions

Processed Aconitum carmichaelii lateral root is derived from the dried lateral root of Aconitum

carmichaelii Debx. (Family Ranunculaceae) after processing (Figure 1).
2 © ISO 2021 – All rights reserved
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ISO/FDIS 23962:2021(E)
Key
A plant of Aconitum carmichaelii Debx. 1 flower
B main root of Aconitum carmichaelii Debx. 2 leaf
C lateral root of Aconitum carmichaelii Debx. 3 stem
D unprocessed Aconitum carmichaelii lateral r
...