Determination of hydroxytyrosol and tyrosol content in extra virgin olive oils — Reverse phase high performance liquid chromatography (RP-HPLC) method

Détermination de la teneur en hydroxytyrosol et tyrosol dans les huiles d'olive vierges extra — Méthode par chromatographie liquide à haute performance en phase inverse (CLHP-RP)

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© ISO 2022 – All rights reserved
ISO/DISPRF 23942:2022(E)
Date: 2022-06-0209-07
ISO/TC 34/SC 11
Secretariat: BSI
Determination of hydroxytyrosol and tyrosol content in extra
virgin olive oils — Reverse phase high performance liquid
chromatography (RP-HPLC) method

Détermination de la teneur en hydroxytyrosol et tyrosol dans les huiles d'olive vierges extra —

Méthode par chromatographie liquide à haute performance en phase inverse (CLHP-PIRP)

---------------------- Page: 1 ----------------------
ISO/PRF 23942:2022(E)
© ISO 2022

All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of

this publication may be reproduced or utilized otherwise in any form or by any means, electronic or

mechanical, including photocopying, or posting on the internet or an intranet, without prior written

permission. Permission can be requested from either ISO at the address below or ISO's member body in the

country of the requester.
ISO Copyright Office
CP 401 • CH-1214 Vernier, Geneva
Phone: + 41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland.
ii © ISO 2022 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/PRF 23942:2022(E)
Contents Page

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

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

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

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

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

4 Principle .............................................................................................................................................................. 1

5 Reagents .............................................................................................................................................................. 1

6 Apparatus ........................................................................................................................................................... 2

7 Sampling ............................................................................................................................................................. 3

8 Procedure ........................................................................................................................................................... 3

8.1 Sample preparation ........................................................................................................................................ 3

8.2 HPLC analysis .................................................................................................................................................... 3

8.2.1 General ................................................................................................................................................................ 3

8.2.2 HPLC conditions ............................................................................................................................................... 3

8.2.3 Peak identification .......................................................................................................................................... 4

9 Expression of results ...................................................................................................................................... 4

10 Precision ............................................................................................................................................................. 5

10.1 Validation study ............................................................................................................................................... 5

10.2 Repeatability, r ................................................................................................................................................. 5

10.3 Reproducibility, R ............................................................................................................................................ 6

11 Test report ......................................................................................................................................................... 6

Annex A (informative) Chromatogram 280 nm ................................................................................................. 7

Annex B (normative) Limit of detection (LOD) and limit of quantification (LOQ) ................................ 8

Annex C (informative) Validation studies ............................................................................................................ 9

Bibliography ................................................................................................................................................................. 13

© ISO 2022 – All rights reserved iii
---------------------- Page: 3 ----------------------
ISO/PRF 23942:2022(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 non-governmental, 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 34, Food products, Subcommittee SC 11,

Animal and vegetable fats and oils.

This first edition cancels and replaces ISO/TS 23942:2020, which has been technically revised.

The main changes are as follows:
— conversion of a Technical Specification to an International Standard;
— additional validation studies have been added to Annex C.

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 2022 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/PRF 23942:2022(E)
Introduction

Biophenolic compounds of a secoiridoid nature, and typical of extra virgin olive oil (Olea europaea L.), are

derived from oleuropein and ligstroside, and are correlated to different beneficial health effects for

human beings other than particular sensorial characteristics. The biophenolic compounds contain, in an

esterified form, two aromatic alcohols, namely hydroxytyrosol and tyrosol. The method given in this

document is based on an extraction of the biophenolic fraction with a methanol/water solution and a

[ [6][7] ]
subsequent hydrolysis reaction to produce free tyrosol and hydroxytyrosol . .
© ISO 2022 – All rights reserved v
---------------------- Page: 5 ----------------------
INTERNATIONAL STANDARD ISO/PRF 23942:2022(E)
Determination of hydroxytyrosol and tyrosol content in extra
virgin olive oils — Reverse phase high performance liquid
chromatography (RP-HPLC) method
1 Scope

This document specifies a method for the quantitative determination of hydroxytyrosol and tyrosol

content in extra virgin olive oils using reverse phase high performance liquid chromatography (RP-HPLC)

with spectrophotometric detection.

The method is also applicable to all other olive oils of a different commercial category.

2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

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

— ISO Online browsing platform: available at https://www.iso.org/obp
— IEC Electropedia: available at https://www.electropedia.org/
3.1
hydroxytyrosol and tyrosol

aromatic alcohols present in extra virgin olive oil typical of Olea europaea L. species as free or bound form

4 Principle

Hydroxytyrosol and tyrosol, present in free and esterified forms, are extracted from the oil with a

methanol/water solution and then submitted to hydrolysis reaction with a 10 % of sulphuric acid

ethanolic solution. The components are identified by means of HPLC and a spectrophotometric detector

at 280 nm. The amount of free aromatic alcohols is calculated with the use of an external standard.

5 Reagents

During the analysis, unless otherwise stated, use only reagents of recognized analytical grade.

5.1 Ortho-phosphoric acid, a volume fraction of 85 %.
5.2 Methanol chromatographic grade.
5.3 Acetonitrile chromatographic grade.
5.4 Water chromatographic grade.
© ISO 2022 – All rights reserved
---------------------- Page: 6 ----------------------
ISO/PRF 23942:2022(E)
5.5 Ethanol, a volume fraction of 96 %.
5.6 Sulphuric acid, a volume fraction of 96 %.
5.7 Methanol/water solution, 80/20 v/v.

5.8 Reference sample: hydroxytyrosol or 2-(3,4-Dihydroxyphenyl)ethanol, e.g. Extrasynthese,

(Cedex, France) .
5.9 Reference sample: tyrosol, e.g. Sigma Aldrich (Germany) .
5.10 Standard calibration solution of hydroxytyrosol and tyrosol.

Prepare the external standard calibration solution of hydroxytyrosol and tyrosol as follows.

Weigh accurately, to the nearest 0,1 mg, about 25 mg of hydroxytyrosol (5.8) and tyrosol (5.9) in a

graduated 50 ml flask (6.2) and make to volume with a solution of methanol/water 80/20 v/v (5.7).

Transfer 1 ml of this solution in another 10 ml flask and fill to volume with the same solution of

methanol/water 80/20 v/v (5.7). The final concentration is 50 mg/l of each external standard. Inject

20 μl of this solution in the HPLC system. The solution is stable for at least six months at –20 °C.

5.11 Hydrolysis solution, consisting of ethanol/water/sulphuric acid 50/40/10 v/v/v.

6 Apparatus
The usual laboratory glassware and the following shall be used.
6.1 Analytical balance suitable for weighing to an accuracy of within ± 0,1 mg.
6.2 10 ml and 50 ml calibrated flasks, class A.
6.3 1 000 μl and 5 000 μl electronic pipette or manual pipette.
6.4 10 ml test tube, with a screw cap.
6.5 Mixer, type vortex.
6.6 Ultrasonic extraction bath.
6.7 PVDF (polyvinyl difluoride) syringe filters, 0,45 μm, 13 mm.
6.8 Centrifuge, able to operate at 5 000 r/min.
6.9 5 ml plastic syringe.
6.10 Thermostatic bath.

6.11 Analytical system, comprising a HPLC ternary pump with a degassing system equipped with an

HPLC column, RP 18 reverse phase. The following column has proven to be adapted for the determination

Extrasynthese (Cedex, France) and Sigma Aldrich (Germany) are examples of a companies that make suitable

products available commercially. This information is given for the convenience of users of this document and does

not constitute an endorsement by ISO of these products.
© ISO 2022 – All rights reserved
---------------------- Page: 7 ----------------------
ISO/PRF 23942:2022(E)

(internal diameter 4,6 mm, length 25 cm, size 5 μm, 100 Å, type Spherisorb ODS2 ) with a UV

spectrophotometric detector at 280 nm and integration system. A photodiode array detector (PDA) for

spectra recording can be used to facilitate peak identification, by matching the hydroxytyrosol and

tyrosol spectra in the sample extract with the spectra of the external standard.
A system for analysis data and integration is needed.
7 Sampling

It is important that an intact oil sample is delivered to the laboratory, which has not been damaged or

modified during transport or storage. A representative sample is considered for the purpose of the

analysis. A recommended sampling method is given in ISO 5555.
8 Procedure
8.1 Sample preparation

Weigh, with an analytical balance (6.1), 2 g of oil well-homogenized in a 10 ml conical test tube (6.4). Add,

using a pipette (6.3), 5 ml of the methanol/water solution 80/20 v/v (5.7). Mix the solution with the help

of a mixer for test tube type vortex (6.5) for 1 min and continue the extraction for 15 min in an ultrasonic

bath (6.6) at room temperature. Centrifuge (6.8) at 4500 rcf5 000 r/min for 25 min. Filter an aliquot

through a PVDF membrane syringe filter (6.7). Transfer 1 ml, using a pipette (6.3), of the filtered solution

into another 10 ml test tube (6.4) and completely dry on a thermostatic bath (6.10) at a maximum

temperature of 40 °C under nitrogen stream. Add 1 ml of hydrolysis solution (5.11) and mix, followed by

reaction at 40 °C for 1 h. Leave the solution at room temperature overnight. Then filter the solution using

a PVDF membrane syringe filter (6.7).
8.2 HPLC analysis
8.2.1 General

Inject 20 µl of the sample into the HPLC system (6.11). The first sample injected as part of a series of

analysis shall be a blank of a methanol/water solution 80/20 v/v (5.7). There shall be no interfering

signals present during the chromatographic run at the same retention time of hydroxytyrosol and tyrosol.

8.2.2 HPLC conditions

The operating conditions given in Table 1 have proven to be adapted for the determination.

Table 1 — Operating conditions
Time Flow A B C
min ml/min % % %
0 1,00 96 2 2
40 1,00 50 25 25
45 1,00 40 30 30

The Spherisorb ODS2 column is an example of suitable chromatographic column that is commercially available.

Alternative columns may be used, such as columns suitable for aan Ultra-HPLC (UHPLC) system, if the operating

conditions in Table 1 isare adjusted and the resulting precision data parameters are equal or better than those

reported in Tables C.3, C.4, and C.5. This information is given for the convenience of users of this document and

does not constitute an endor
...

INTERNATIONAL ISO
STANDARD 23942
First edition
Determination of hydroxytyrosol
and tyrosol content in extra virgin
olive oils — Reverse phase high
performance liquid chromatography
(RP-HPLC) method
Détermination de la teneur en hydroxytyrosol et tyrosol dans les
huiles d'olive vierges extra — Méthode par chromatographie liquide à
haute performance en phase inverse (CLHP-RP)
PROOF/ÉPREUVE
Reference number
ISO 23942:2022(E)
© ISO 2022
---------------------- Page: 1 ----------------------
ISO 23942:2022(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2022

All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may

be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on

the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below

or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
PROOF/ÉPREUVE © ISO 2022 – All rights reserved
---------------------- Page: 2 ----------------------
ISO 23942:2022(E)
Contents Page

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

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

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

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

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

4 Principle ........................................................................................................................................................................................................................ 1

5 Reagents ........................................................................................................................................................................................................................ 1

6 Apparatus .................................................................................................................................................................................................................... 2

7 Sampling ....................................................................................................................................................................................................................... 3

8 Procedure ....................................................................................................................................................................................................................3

8.1 Sample preparation ............................................................................................................................................................................ 3

8.2 HPLC analysis .......................................................................................................................................................................................... 3

8.2.1 General ........................................................................................................................................................................................ 3

8.2.2 HPLC conditions .................................................................................................................................................................. 3

8.2.3 Peak identification ............................................................................................................................................................ 4

9 Expression of results ....................................................................................................................................................................................... 4

10 Precision ....................................................................................................................................................................................................................... 5

10.1 Validation study ..................................................................................................................................................................................... 5

10.2 Repeatability, r........................................................................................................................................................................................ 6

10.3 Reproducibility, R ................................................................................................................................................................................. 6

11 Test report .................................................................................................................................................................................................................. 6

Annex A (informative) Chromatogram 280 nm ....................................................................................................................................... 7

Annex B (normative) Limit of detection (LOD) and limit of quantification (LOQ) .............................................8

Annex C (informative) Validation studies ...................................................................................................................................................... 9

Bibliography .............................................................................................................................................................................................................................13

iii
© ISO 2022 – All rights reserved PROOF/ÉPREUVE
---------------------- Page: 3 ----------------------
ISO 23942:2022(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 non-governmental, 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 34, Food products, Subcommittee SC 11,

Animal and vegetable fats and oils.

This first edition cancels and replaces ISO/TS 23942:2020, which has been technically revised.

The main changes are as follows:
— conversion of a Technical Specification to an International Standard;
— additional validation studies have been added to Annex C.

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.
PROOF/ÉPREUVE © ISO 2022 – All rights reserved
---------------------- Page: 4 ----------------------
ISO 23942:2022(E)
Introduction

Biophenolic compounds of a secoiridoid nature, and typical of extra virgin olive oil (Olea europaea L.),

are derived from oleuropein and ligstroside, and are correlated to different beneficial health effects for

human beings other than particular sensorial characteristics. The biophenolic compounds contain, in

an esterified form, two aromatic alcohols, namely hydroxytyrosol and tyrosol. The method given in this

document is based on an extraction of the biophenolic fraction with a methanol/water solution and a

[6][7]
subsequent hydrolysis reaction to produce free tyrosol and hydroxytyrosol.
© ISO 2022 – All rights reserved PROOF/ÉPREUVE
---------------------- Page: 5 ----------------------
INTERNATIONAL STANDARD ISO 23942:2022(E)
Determination of hydroxytyrosol and tyrosol content in
extra virgin olive oils — Reverse phase high performance
liquid chromatography (RP-HPLC) method
1 Scope

This document specifies a method for the quantitative determination of hydroxytyrosol and tyrosol

content in extra virgin olive oils using reverse phase high performance liquid chromatography

(RP-HPLC) with spectrophotometric detection.

The method is also applicable to all other olive oils of a different commercial category.

2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

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

— ISO Online browsing platform: available at https:// www. iso. org/o bp
— IEC Electropedia: available at https:// www.e lectropedia. org/
3.1
hydroxytyrosol and tyrosol

aromatic alcohols present in extra virgin olive oil typical of Olea europaea L. species as free or bound

form
4 Principle

Hydroxytyrosol and tyrosol, present in free and esterified forms, are extracted from the oil with

a methanol/water solution and then submitted to hydrolysis reaction with a 10 % of sulphuric acid

ethanolic solution. The components are identified by means of HPLC and a spectrophotometric detector

at 280 nm. The amount of free aromatic alcohols is calculated with the use of an external standard.

5 Reagents

During the analysis, unless otherwise stated, use only reagents of recognized analytical grade.

5.1 Ortho-phosphoric acid, a volume fraction of 85 %.
5.2 Methanol chromatographic grade.
5.3 Acetonitrile chromatographic grade.
5.4 Water chromatographic grade.
© ISO 2022 – All rights reserved PROOF/ÉPREUVE
---------------------- Page: 6 ----------------------
ISO 23942:2022(E)
5.5 Ethanol, a volume fraction of 96 %.
5.6 Sulphuric acid, a volume fraction of 96 %.
5.7 Methanol/water solution, 80/20 v/v.

5.8 Reference sample: hydroxytyrosol or 2-(3,4-Dihydroxyphenyl)ethanol, e.g. Extrasynthese,

(Cedex, France) .
5.9 Reference sample: tyrosol, e.g. Sigma Aldrich (Germany) .
5.10 Standard calibration solution of hydroxytyrosol and tyrosol.

Prepare the external standard calibration solution of hydroxytyrosol and tyrosol as follows.

Weigh accurately, to the nearest 0,1 mg, about 25 mg of hydroxytyrosol (5.8) and tyrosol (5.9) in a

graduated 50 ml flask (6.2) and make to volume with a solution of methanol/water 80/20 v/v (5.7).

Transfer 1 ml of this solution in another 10 ml flask and fill to volume with the same solution of

methanol/water 80/20 v/v (5.7). The final concentration is 50 mg/l of each external standard. Inject

20 μl of this solution in the HPLC system. The solution is stable for at least six months at –20 °C.

5.11 Hydrolysis solution, consisting of ethanol/water/sulphuric acid 50/40/10 v/v/v.

6 Apparatus
The usual laboratory glassware and the following shall be used.
6.1 Analytical balance suitable for weighing to an accuracy of within ± 0,1 mg.
6.2 10 ml and 50 ml calibrated flasks, class A.
6.3 1 000 μl and 5 000 μl electronic pipette or manual pipette.
6.4 10 ml test tube, with a screw cap.
6.5 Mixer, type vortex.
6.6 Ultrasonic extraction bath.
6.7 PVDF (polyvinyl difluoride) syringe filters, 0,45 μm, 13 mm.
6.8 Centrifuge, able to operate at 5 000 r/min.
6.9 5 ml plastic syringe.
6.10 Thermostatic bath.

6.11 Analytical system, comprising a HPLC ternary pump with a degassing system equipped

with an HPLC column, RP 18 reverse phase. The following column has proven to be adapted for the

1) Extrasynthese (Cedex, France) and Sigma Aldrich (Germany) are examples of a companies that make suitable

products available commercially. This information is given for the convenience of users of this document and does

not constitute an endorsement by ISO of these products.
PROOF/ÉPREUVE © ISO 2022 – All rights reserved
---------------------- Page: 7 ----------------------
ISO 23942:2022(E)

determination (internal diameter 4,6 mm, length 25 cm, size 5 μm, 100 Å, type Spherisorb ODS2 ) with

a UV spectrophotometric detector at 280 nm and integration system. A photodiode array detector (PDA)

for spectra recording can be used to facilitate peak identification, by matching the hydroxytyrosol and

tyrosol spectra in the sample extract with the spectra of the external standard.
A system for analysis data and integration is needed.
7 Sampling

It is important that an intact oil sample is delivered to the laboratory, which has not been damaged

or modified during transport or storage. A representative sample is considered for the purpose of the

analysis. A recommended sampling method is given in ISO 5555.
8 Procedure
8.1 Sample preparation

Weigh, with an analytical balance (6.1), 2 g of oil well-homogenized in a 10 ml conical test tube (6.4).

Add, using a pipette (6.3), 5 ml of the methanol/water solution 80/20 v/v (5.7). Mix the solution with

the help of a mixer for test tube type vortex (6.5) for 1 min and continue the extraction for 15 min

in an ultrasonic bath (6.6) at room temperature. Centrifuge (6.8) at 5 000 r/min for 25 min. Filter

an aliquot through a PVDF membrane syringe filter (6.7). Transfer 1 ml, using a pipette (6.3), of the

filtered solution into another 10 ml test tube (6.4) and completely dry on a thermostatic bath (6.10) at a

maximum temperature of 40 °C under nitrogen stream. Add 1 ml of hydrolysis solution (5.11) and mix,

followed by reaction at 40 °C for 1 h. Leave the solution at room temperature overnight. Then filter the

solution using a PVDF membrane syringe filter (6.7).
8.2 HPLC analysis
8.2.1 General

Inject 20 µl of the sample into the HPLC system (6.11). The first sample injected as part of a series of

analysis shall be a blank of a methanol/water solution 80/20 v/v (5.7). There shall be no interfering

signals present during the chromatographic run at the same retention time of hydroxytyrosol and

tyrosol.
8.2.2 HPLC conditions

The operating conditions given in Table 1 have proven to be adapted for the determination.

2) The Spherisorb ODS2
...

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