Comparison of European US Japanese Pharmacopoeia

MEDICAL GASES
COMPARISON OF EUROPEAN,
US & JAPANESE
PHARMACOPOEIA
MONOGRAPHS
FOR MEDICINAL GASES
MGC Doc 152/11/E
Revision of Doc 152/08
EUROPEAN INDUSTRIAL GASES ASSOCIATION AISBL

AVENUE DES ARTS 3-5 B 1210 BRUSSELS
Tel : +32 2 217 70 98 Fax : +32 2 219 85 14
E-mail : info@eiga.eu Internet : www.eiga.eu
Doc 152/11
COMPARISON OF
EUROPEAN, US & JAPANESE PHARMACOPOEIA
MONOGRAPHS FOR MEDICINAL GASES
PREPARED BY :
Atoosa Bayat
Linde
Peter Henrys
Linde
Stefania Mariani
SOL
Ichirou Nakayama
JIMGA (Nippon Sanso Corp)
Peter Neu
Air Liquide
Martin Schfnagl
Messer Group
Franois Simondet
Air Liquide
Francisco Revuelta
Praxair
Jan Strybol
Air Products
Andy Webb
EIGA
Disclaimer
All technical publications of EIGA or under EIGA's name, including Codes of practice, Safety procedures and any other technical
information contained in such publications were obtained from sources believed to be reliable and are based on technical
information and experience currently available from members of EIGA and others at the date of their issuance.
While EIGA recommends reference to or use of its publications by its members, such reference to or use of EIGA's publications by
its members or third parties are purely voluntary and not binding.
Therefore, EIGA or its members make no guarantee of the results and assume no liability or responsibility in connection with the
reference to or use of information or suggestions contained in EIGA's publications.
EIGA has no control whatsoever as regards, performance or non performance, misinterpretation, proper or improper use of any
information or suggestions contained in EIGA's publications by any person or entity (including EIGA members) and EIGA expressly
disclaims any liability in connection thereto.
EIGA's publications are subject to periodic review and users are cautioned to obtain the latest edition.
EIGA 2011 - EIGA grants permission to reproduce this publication provided the Association is acknowledged as the source
EUROPEAN INDUSTRIAL GASES ASSOCIATION AISBL
Avenue des Arts 3-5 B 1210 Brussels
Tel +32 2 217 70 98
Fax +32 2 219 85 14
Internet: www.eiga.eu
E-mail: info@eiga.eu
MGC
DOC 152/11
Table of Contents
Introduction ...................................................................................................................................... 1
Scope and purpose .......................................................................................................................... 1

2.1
2.2
Scope ........................................................................................................................................ 1
Purpose .................................................................................................................................... 1
Specifications and test methods ...................................................................................................... 2

3.1
European Pharmacopoeia test requirements ........................................................................... 3
Currency of Information ................................................................................................................... 4
Comparison tables ........................................................................................................................... 4

5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8
5.9
5.10
5.11
5.12
5.13
Medical Oxygen ........................................................................................................................ 5

93% Oxygen ............................................................................................................................. 6
Nitrous Oxide ............................................................................................................................ 7
Nitrogen .................................................................................................................................... 8
97% Nitrogen ............................................................................................................................ 9
Low Oxygen Nitrogen ............................................................................................................. 10
Carbon Dioxide ....................................................................................................................... 11
Medicinal Air ........................................................................................................................... 12
Synthetic Medicinal Air ........................................................................................................... 13
Helium ................................................................................................................................. 14
Nitric Oxide.......................................................................................................................... 15
Argon ................................................................................................................................... 16
Carbon Monoxide ................................................................................................................ 17
Japanese Pharmacopoeia ............................................................................................................. 18

6.1
6.2
6.3
6.4
Medical Oxygen ...................................................................................................................... 18

Nitrous Oxide .......................................................................................................................... 19
Carbon Dioxide ....................................................................................................................... 20
Nitrogen .................................................................................................................................. 21
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Introduction
There are three prime regional Pharmacopoeia organisations that are responsible for the preparation
and publication of Pharmacopoeia monographs, covering the commonly used substances involved in
the manufacture and supply of medicinal products.
The three prime organisations are:
European Directorate for the Quality of Medicines (EDQM) - responsible for the European
Pharmacopeia (Ph Eur) monographs
United States Pharmacopeial Convention - responsible for the US Pharmacopoeia (USP)
Ministry of Health and Welfare - responsible for the Japanese Pharmacopoeia (JP)
The three Pharmacopoeias have monographs for a number of medical / medicinal gases. These
gases can be used either as active ingredients in medicinal products or excipients, used in the
manufacture of medical gas mixtures, administered to patients. Alternatively, they can be used as
pharmaceutical gases, used in the manufacture, storage or distribution of all medicinal products.
The purpose of these monographs is to specify for each gas:
the minimum assay / purity for the product that is suitable for medicinal use
the maximum level of defined impurities, that could have an adverse effect on the patient
the appropriate test methods for determining quality of the product.
This document provides a comparison between the specifications and the test methods defined in
each of the regional pharmacopoeia compendiums.
2
Scope and purpose
2.1
Scope
This document covers the pharmacopoeia monographs for medicinal and pharmaceutical gases
published by the:
European Pharmacopoeia (Ph Eur)

United States Pharmacopeia (USP)
Japanese Pharmacopoeia (JP)
It includes the monographs for gases used in the manufacture and supply of medicinal products
including:
Medicinal gases, which are used as active ingredients in medical gases and gas mixtures
supplied for patient use
Excipient gases, which are added to gas mixtures but have no therapeutic effects
Pharmaceutical gases, which are specified in the manufacture, storage and distribution of
medicinal products.
The comparison tables in the Appendix provide a comparison between the European and the United
States Pharmacopoeia monographs for all of the specified gases.
A separate table is included to detail the monographs published by the Japanese Pharmacopoeia,
where the monographs do not specify acceptance limits and only provide test criteria for compliance.
2.2
Purpose
The purpose of the document is to provide a simple cross reference between the three sets of
published monographs to enable a comparison of the requirements for each method.
This is intended to demonstrate compliance between monographs but should not be used as a
detailed method of carrying out the relevant tests.
Where the testing to a specific monograph is required, the user should refer to the original document
(and all supporting documents within the relevant pharmacopoeia) to ensure that the tests are carried
out correctly.
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DOC 152/11
Specifications and test methods
The most commonly used medicinal gases have been included in the Pharmacopoeia for many years
but recently a number of new medical gases have been added.
The following table gives a quick reference for the different gases that have been covered by
published monographs in the three Pharmacopoeias:
Gases
Monograph Reference
European
US
Japanese
Pharmacopoeia
Pharmacopoeia
Pharmacopoeia
Medical Oxygen
0417
7782-44-7
No Reference No.
Oxygen 93%
2455
No Reference No.
NS
Nitrous Oxide
0416
10024-97-2
No Reference No.
Nitrogen
1247
7727-37-9
No Reference No.
NS
No Reference No.
NS
Low Oxygen Nitrogen
1685
NS
NS
Carbon Dioxide
0375
124-38-9
No Reference No.
Medicinal Air
1238
No Reference No.
NS
Synthetic Medicinal Air
1684
NS
NS
Helium
2155
7440-59-7
NS
Nitric Oxide
1550
NS
NS
Argon
2407
IP
NS
IP
IP
NS
2408
IP
NS
Nitrogen 97%
Methane
Carbon Monoxide
NS:
IP:
Not specified
In preparation
Each monograph defines the specification of the medicinal gas, including the:
assay of the product;
maximum allowable impurity levels for those contaminants specified in the product;
approved analytical method for identifying the gas;
approved analytical method for determining the assay, and
approved analytical test method for determining each contaminant specified within the
monograph.
The validated analytical methods described in the monographs are the official test methods upon
which the specifications in the relevant Pharmacopoeia are based.
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DOC 152/11
European Pharmacopoeia test requirements
For the European Pharmacopoeia, the test methods are verified against the protocols set out in the
ICH Guidelines for accuracy and precision, linearity and range and specificity. The results also need
to conform to the requirements of repeatability and peak symmetry.
In addition to the specific medicinal gas monographs there are several general notices that apply to all
monographs.
The following general test methods are particularly applicable to the analysis of medical gases:
Test Reference
Test Method
2.1.6
Gas Detector Tubes
2.2.28
Gas Chromatography
2.2.46
Chromatographic Separation Techniques
2.5.24
Carbon Dioxide in Gases
2.5.25
Carbon Monoxide in Gases
2.5.26
Nitrogen Monoxide and Nitrogen Dioxide in Gases
2.5.27
Oxygen in Gases
2.5.28
Water in Gases
Alternative methods of analysis may be used for testing medical gases, after agreement with the
competent authority, provided that the test methods have been validated in line with the ICH protocols
to demonstrate that they are equivalent to the specified methods.
The European Pharmacopoeia monographs test methods specified for medical gases are divided into
two main sections:
Production
Tests
The PRODUCTION methods are intended to be the methods used by the manufacturers. These
methods are the basis for the release of the product at the manufacturers site for patient use. The
methods specified in the PRODUCTION section of the monograph normally utilise the latest analytical
instruments, that should be available to the manufacturers of the gases.
The TEST methods are intended to be the methods used by the end user to assure themselves that
the medical gases are of the appropriate quality. For example, these could be used for routine testing
by the Pharmacist at the hospital of the pipeline gases at the terminal outlets in the hospital. The
TEST methods generally utilise detector tubes for the test method as it is unlikely that the end users
would have all of the appropriate analytical instruments available to them for testing.
Where the hospital is the manufacturer, for example where they are producing medicinal air on site
using an air compressor, the PRODUCTION test methods should be applied.
The United States and Japanese Pharmacopoeia monographs only specify one method for the
analysis of the medical gas.
These test methods utilise either detector tubes or wet chemistry techniques as the approved test
method. The Japanese Pharmacopoeia monographs only detail the test methods and do not give the
values of the specification limits in percentage terms or parts per million.
In all cases the test methods specified in the monographs should have been validated. For the
European Pharmacopoeia, this work is normally undertaken by one of the national representative on
the relevant Pharmacopoeia committee.
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Currency of Information
The version of the relevant Pharmacopoeias used to provide the information for the comparison
tables is:
European Pharmacopoeia:
United States Pharmacopoeia:
Japanese Pharmacopoeia:
7.0 (July 2010)

USP33, NF28 (2010)
15 (April 2006)
As and when there are relevant changes to any of these monographs this comparison document will
be updated. However, where it is important that the latest information is available, the original
Pharmacopoeia document should be referenced to ensure that there have been no revisions to the
individual monograph.
5
Comparison tables
The following tables provide a comparison between the European and US Pharmacopoeia
monographs for each of the specified medicinal or pharmaceutical gas.
MGC
5.1
DOC 152/11
Medical Oxygen
Oxygen
Monograph
Ph Eur
USP
Name
Oxygen
Oxygen
0417
7782-44-7
O2
O2
Reference
Chemical Formula
Oxygen contains not less than

99.5% V/V of O2.
Definition
Identification
It is produced by a purification
process followed by the distillation
of the liquefied ambient air
Complies with the Assay
Oxygen contains not less than

99.0% V/V of O2 .
(Note: Oxygen produced by the airliquefaction is exempt from the
requirements of CO and CO2
testing)
Distinction from CO2 detector tube
Assay
Production
Specification
Analytical Method
99.5% V/V O2
99.0 % V/V O2
Paramagnetic Analyser
Volumetric Gas Absorption

Apparatus
5 ppm V/V
0.001% V/V
Infrared analyser
Detector tube
300 ppm V/V
0.03% V/V
Infrared analyser
Detector tube
CO
Limit
CO2
Limit
Odour H2O
Impurities
Limit
Analytical Method
Analytical Method
Analytical Method
Limit
Analytical Method
67 ppm V/V
Electrolytic hygrometer
Not Specified
Not Specified
No odour
Organoleptic
Tests
CO
Analytical Method
Detector Tube
CO2
Limit
300 ppm V/V
Analytical Method
Detector Tube
H2O
5 ppm V/V
Limit
Limit
67 ppm V/V
Analytical Method
Detector Tube
No Tests Section specified
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5.2
DOC 152/11
93% Oxygen
Oxygen 93
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
USP
Oxygen (93 per cent)
Oxygen 93 Percent
2455
Not Specified
O2
O2
Oxygen 93 is Oxygen produced from
Oxygen 93% contains between
Air by molecular sieve process.
90.0%V/V and 96% V/V of O2.
Remainder mainly consists of argon Contains not less than 90.0 % V/V
and nitrogen.
and not more than 96 % O2 V/V, the
Monograph applies to oxygen used Remainder consists of mostly Argon
on the site where produced. It does and Nitrogen
not apply to individual concentrators.
Complies with the Assay.
Complies with the Assay.
Distinction from CO2 (detector tube)
Assay
Production
Specification
Analytical Method
90.0% O2 96.0% V/V O2
90.0% O2 96.0% V/V O2
Paramagnetic analyser
Volumetric Gas Absorption
5 ppm V/V
Infrared analyser
0.001 % V/V
Detector tube
300 ppm V/V

Infrared analyser
0.03 % V/V
Detector tube
67 ppm V/V
Not Specified
CO
Limit
CO2
Limit
NO/
Odour H2O
NO2
Limit
SO2
Limit
Oil
Impurities
Limit
Analytical Method
Analytical Method
Analytical Method
Limit
No odour
Analytical Method
Limit
Analytical Method
Analytical Method
Organoleptic
2 ppm V/V in total
Chemiluminescence Analyser
1 ppm V/V
UV Fluorescence Analyser
Analytical Method
0.1 mg/m3
Detector Tube
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
5 ppm V/V
Detector Tube
300 ppm V/V
Detector Tube
67 ppm V/V
Detector Tube
2 ppm V/V
Detector Tube
1 ppm V/V
Detector Tube
0.1 mg/m3
Detector Tube
Not Specified
Oil
SO2
NO/
NO2
H2O
CO2
CO
Tests
No specific Tests Section
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Nitrous Oxide
Nitrous Oxide
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
USP
Nitrous Oxide
Nitrous Oxide
0416
10024-97-2
N2O
Contains not less than 98.0% V/V
of N2O in the gaseous phase, when
sampled at 15C.
Complies with the assay.
or - Place a glowing splinter of
wood in the substance to be
examined. The splinter bursts into
flame.
or - Introduce the substance to be
examined into alkaline pyrogallol
solution R. A brown colour does
not develop.
N2O
Nitrous Oxide contains not less
than 99.0% V/V of N2O
Comparison of pressure between
N2O container and certified
standard.
Distinction from CO2 detector tube.
Distinction from O2
(alkaline pyrogallol solution)
Assay
Production
Assay
Analytical Method
98.0% V/V N2O

Measured in gas phase at 15OC
Infrared analyser
1.0% air indicating

99.0% V/V of N2O
Gas Chromatography
5 ppm V/V
0.001% V/V
Gas Chromatography
Detector tube
CO
Limit
CO2
Limit
NO/
NO2
Limit
H2O
Limit
HaloNH3
gens
Impurities
Limit
Analytical Method
Analytical Method
Analytical Method
Analytical Method
Analytical Method
Limit
Analytical Method
300 ppm V/V
0.03% V/V
Gas Chromatography
2 ppm V/V in total in the gaseous
and liquid phases
Detector tube
NO 1ppm, NO2 1ppm
67 ppm V/V
150 mg/m3
Detector Tube
Not Specified
Not Specified
Detector Tube
0.0025 % V/V
Detector Tube
1ppm
Detector Tube
Limit
5 ppm V/V
300 ppm V/V
Analytical Method
Detector Tube
CO2
Detector Tube
Limit
NO/
NO2
Analytical Method
Limit
Analytical Method
Detector Tube
H2O
CO
Tests
Limit
67 ppm V/V
Analytical Method
Detector Tube
2 ppm V/V
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5.4
DOC 152/11
Nitrogen
Ph Eur
Nitrogen
1247
N2
Nitrogen contains not less than
99.5% V/V of N2.
Retention time of peak with Gas
Chromatography
or Place a glowing splinter of wood
in the substance to be
examined. The splinter is
extinguished.
or Test with magnesium turnings
USP
Nitrogen
7727-37-9
N2
Nitrogen contains not less than
99.0%,by volume of N2
Extinguishing of burning wood
splinter in a Nitrogen test tube.
Assay
99.5% V/V N2
Analytical Method
Gas Chromatography
1.0% O2 indicates 99.0% V/V of

N2
Gas Chromatography
CO
5 ppm V/V
Infrared analyser
0.001 % V/V
Detector tube
CO2
Nitrogen
Monograph
Name
Reference
Chemical Formula
300 ppm V/V

Infrared analyser
Not specified
Definition
Identification
Assay
Production
Odour H2O
O2
Impurities
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
50 ppm V/V
Oxygen Analyser with
electrochemical cell
67 ppm V/V
1.0 %
Determined in Assay
Not specified
No odour
Not specified
Organoleptic
5 ppm V/V
Analytical Method
Detector Tube
CO2
Limit
300 ppm V/V
Analytical Method
Detector Tube
Limit
Analytical Method
67 ppm V/V
Detector Tube
CO
Limit
H2O
Tests
MGC
5.5
DOC 152/11
97% Nitrogen
Nitrogen 97%
Monograph
Name
Reference
Ph Eur
No equivalent European
Pharmacopoeia monograph
Chemical Formula
USP
Nitrogen 97 Percent
Not Specified
N2
Definition
Nitrogen 97 Percent is Nitrogen

produced from Air by physical
separation.
Contains not less than 97.0% N2
V/V
Identification
Extinguishing of burning wood

splinter in a Nitrogen test tube.
Assay
Production
3.0% O2 indicates 97.0% V/V of
N2
Assay
Analytical Method
Gas Chromatography
CO
Limit
0.001 % V/V
Analytical Method
Detector tube
CO2
Limit
0.03 % V/V
Analytical Method
Detector tube
SO2
Limit
5 ppm V/V
Analytical Method
Detector tube
NO/
NO2
Impurities
Limit
2.5 ppm V/V
Analytical Method
Detector Tube
3.0 % V/V
Odour
O2
Limit
Gas Chromatography
(determined in the Assay)
Analytical Method
Limit
No odour
Analytical Method
Organoleptic
Tests
Limit
Analytical Method
MGC
5.6
DOC 152/11
Low Oxygen Nitrogen
Low Oxygen Nitrogen

USP
No equivalent US Pharmacopoeia
monograph
Monograph
Ph Eur
Name
Nitrogen Low Oxygen
Reference
1685
Chemical Formula
N2
Definition
This monograph applies to

Nitrogen which is used for inerting
finished medicinal products
sensitive to degradation by oxygen.
Does not necessarily apply to N2
used in earlier production steps of
pharmaceutical manufacturing.
Identification
Examine the chromatograms

obtained in the test for impurities.
or - Flame of burning wood splinter
in a Nitrogen test tube/ Test with
magnesium turnings.
Assay
Production
Assay
99.5% V/V N2
Analytical Method
Gas Chromatography
O2
Impurities
Limit
5 ppm V/V O2
Analytical Method

Limit
No Test Section specified
Tests
10
MGC
5.7
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Carbon Dioxide
Carbon Dioxide
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
USP
Carbon Dioxide
Carbon Dioxide
0375
124-38-9
CO2
Carbon Dioxide contains not less
than 99.5% V/V of CO2.in gaseous
phase.
Infrared absorption
spectrophotometry
CO2
Carbon Dioxide contains not less
than 99.0%,by volume of CO2
Carbon Dioxide Detector Tube
or - Glowing wood splinter

extinguished
or - test with magnesium turnings
Assay
Production
Assay
99.5% V/V CO2
Analytical Method
Infrared analyser
99.0% V/V of CO2

Determined with volumetric gas
absorption apparatus
SO2
H2S
NH3
H2O
Total
Sulfur
NO/
NO2
CO
Impurities
Limit
Analytical Method
Limit
5 ppm V/V
Gas Chromatography
2 ppm V/V in total (in gas phase)
0.001% V/V
Detector tube
2.5 ppm (in liquid phase)
specifies 2.5 ppm for each species.
Detector tube
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
67 ppm V/V
150 mg/m3
Detector tube
Not Specified
0.0025 % V/V
Detector tube
1 ppm V/V
Not Specified
Not Specified
Not Specified
1 ppm
Detector tube
5 ppm
Detector tube
Tests
CO
SO2
Limit
H2S
Limit
NO/
NO2
Limit
Analytical Method
Detector Tube
H2O
5 ppm V/V
Limit
Limit
67 ppm V/V
Analytical Method
Detector Tube
Analytical Method
Detector Tube
2 ppm V/V
Analytical Method
Detector Tube
1 ppm V/V
Detector Tube
Analytical Method
2 ppm V/V
11
MGC
5.8
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Medicinal Air
Medicinal Air
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
USP
Air, Medicinal
Medical Air
1238
N/A
N/A
Compressed ambient air containing Natural or synthetic mixture
consisting largely of N2 and O2,
not less than 20.4 %V/V and not
containing not less than 19.5% and
more than 21.4 % V/V of O2.
not more than 23.5% V/V of O2.
or Glowing wood splinter not
extinguished
or Oxygen content tested by
passing sample through
potassium hydroxide/sodium
dithionite solution.
Assay
Production
Assay
Analytical Method
20.4%V/V O2 21.4 % V/V

Paramagnetic Analyser
19.5% V/V O2 23.5% V/V

Odo
ur
H2O
Oil
NO/
NO2
SO2
CO2
CO
Impurities
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
5 ppm V/V
Infrared Analyser
0.001% V/V
Detector tube
500 ppm V/V

Infrared Analyser
0.05% V/V
Detector tube
1 ppm V/V
5 ppm V/V
Detector tube
2 ppm V/V in total

2.5 ppm V/V

Detector Tube
3
No condensate on mirror
0.1 mg/m
Detector tube when an oil lubricated Pass gas slowly over stainless steel
Analytical Method
compressor is used for production
mirror
Limit
No condensate on mirror
67 ppm V/V
Pass gas slowly over stainless steel
Analytical Method
mirror
No odour
Limit
Not specified
Analytical Method
Organoleptic
H2O Oil
NO/
SO2 CO2 CO
NO2
Tests
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
5 ppm V/V
Detector Tube
500 ppm V/V
Detector Tube
1 ppm V/V
Detector Tube
2 ppm V/V
Detector Tube
0.1 mg/m3
Detector Tube
67 ppm V/V
Detector Tube
12
No Specific Tests Section
MGC
5.9
DOC 152/11

Monograph
Name
Reference
Chemical Formula
Definition
Identification
USP
Ph Eur
Air, Synthetic Medicinal
monograph specified
1684
N/A
Gas mixture of N2 (Ph.Eur) and O2
(Ph.Eur) containing between 95.0
% to 105.0 % of the nominal value
which is between 21.0 % V/V to
22.5 % V/V of O2.
or Glowing wood splinter not
extinguished
or Oxygen content tested by
passing sample through
potassium hydroxide/sodium
dithionite solution.
Assay
Production
Assay
Analytical Method
H2O
H2O
Impurities
Limit
Analytical Method
Tests
Containing between 95.0% to

105.0% of the nominal value which
is between 21.0 % V/V to 22.5 %
V/V of O2.
Paramagnetic analyser
67 ppm V/V O2
Limit
67 ppm V/V O2
Analytical Method
Detector Tube
13
MGC
DOC 152/11
5.10 Helium
Helium
Monograph
Name
Reference
Chemical Formula
Definition
Ph Eur
Helium
2155
He
Helium contains not less than 99.5
% V/V of He.
Applies to helium obtained by
separation from natural gas supplies.
USP
Helium
7440-59-7
He
Helium contains not less than 99.0
% V/V of He
99.5 % V/V He
99.0 % V/V He
Identification
The flame of a burning splinter of

wood is extinguished.
A small balloon filled with helium
shows decided buoyancy
Assay
Production
Specification
Analytical Method Gas Chromatography
Gas chromatography
CH4
Impurities
Limit
50 ppm V/V
Analytical Method Infrared analyser
H2O O2
Limit
CO
50 ppm V/V
Electrochemical Cell
Not Specified
67 ppm V/V
Analytical Method Electrolytic hygrometer
Limit
Limit
Analytical Method
Limit
Air
Not Specified
Analytical Method
Not Specified
Not Specified
0.001 % V/V
Detector Tube
Not Specified
1.0 % V/V
Determined in the Assay
No odour
Odour
Limit
Analytical Method
Not Specified
Organoleptic
Tests
Limit
Analytical Method
14
MGC
DOC 152/11
5.11 Nitric Oxide

Nitric Oxide
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
Nitric Oxide
1550
NO
Nitric oxide contains not less than
99.0% V/V of NO.
Examine by infrared spectrometry
and compare with the reference
spectrum
Production
Specification
99.0 % V/V NO
H2O N2O NO2 N2
CO2
Assay
Determine content of NO by
difference using the mass balance
Analytical Method equation after determining the sum
of the impurities described under
production.
Impurities
Limit
3000 ppm V/V
Limit
3000 ppm V/V
Limit
400 ppm V/V
Analytical Method UV Spectrophotometry Analyser
Limit
3000 ppm V/V
Limit
100 ppm V/V
Analytical Method Electrolytic Hygrometer
Tests
Limit
Analytical Method
15
USP
monograph specified
MGC
5.12
DOC 152/11
Argon
Argon
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
USP
Argon
monograph specified
07/2010:2407
Ar
Gas obtained by fractional
distillation. Argon contains not less
than 99.995% v/v of Ar calculated by
deduction of the sum of impurities
found when performing the test for
impurities and water content..
Gas chromatography and verify that
the gas is not oxygen using a
paramagnetic analyser.
Assay
Production
Specification
Impurities
Limit
Analytical Method
Limit
Analytical Method
Tests
Limit
Analytical Method
H2O O2
99.995 % V/V Ar
5 ppm V/V
Gas Chromatography
10 ppm V/V
Electrolytic Hygrometer
16
MGC
DOC 152/11
5.13 Carbon Monoxide

Carbon Monoxide
Monograph
Name
Reference
Chemical Formula
Definition
Identification
Ph Eur
USP
Carbon Monoxide
monograph specified
01/2011:2408
CO
Gas obtained by steam reforming
(catalytic oxidation) of hydrocarbons.
Carbon monoxide contains not less
than 99.5% V/V of CO.
Infrared absorption
spectrophotometry or it complies
with the limits of the assay.
Assay
Production
Specification
Analytical Method Infrared analyser
Nickel tetracarbonyl /
H2
Iron pentacarbonyl
CH4 CO2
Impurities
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
Limit
Analytical Method
H2O
99.5 % V/V CO
300 ppm V/V

Gas Chromatography
100 ppm V/V
Gas Chromatography
300 ppm V/V
Gas Chromatography
Not detectable
Detector tube
Limit
10 ppm V/V
Analytical Method Electrolytic Hygrometer
Tests
Limit
Analytical Method
17
MGC
DOC 152/11
Japanese Pharmacopoeia
6.1
Medical Oxygen
Oxygen
Monograph
JP
Name
Medical Oxygen
Chemical Formula
O2
Definition
Oxygen contains not less than 99.5%vol of O2.
Description
Oxygen is a colourless, odourless gas.

1.
Identification
2.
Put a glowing splinter of wood into the oxygen: it bursts into flames
immediately
The retention time of the principle peak for oxygen coincides with that
of oxygen for chromatography
CO2
Chloride
Oxidising
Substances
Acidity or
alkalinity
Purity
Limit
Colour of the test solution is not deeper than the reference solutions
Analytical Method
Pass through methyl red and bromothymol blue acidified solution in a

Nessler tube. Compare colour against control solution
Limit
The colour is the same as the control solution
Analytical Method
Pass through potassium iodide-starch solution in a Nessler tube. Compare

colour against control solution
Limit
Turbidity produced does not exceed that produced in the control solution
(can be calculated by the method)
Analytical Method
Pass through silver nitrate solution in a Nessler tube. Compare turbidity

against control solution
Limit
Analytical Method
N2
Limit
Analytical Method
Pass through barium hydroxide in a Nessler tube. Compare turbidity against

a control solution of barium hydroxide containing hydrogen carbonate
The peak area of nitrogen in the oxygen is not larger than that of the control
sample
Gas Chromatography
Assay
Assay
Specification
99.5% vol of O2.
Analytical Method
Volumetric Gas Absorption Apparatus
18
MGC
6.2
DOC 152/11
Nitrous Oxide
Nitrous Oxide
Monograph
JP
Name
Nitrous Oxide
Chemical Formula
N2O
Definition
Nitrous oxide contains not less than 97 vol% of N2O
Description
Identification
Nitrous oxide is a colourless, odourless gas at room temperature and at

atmospheric pressure.
1 Put a glowing splinter of wood into nitrous oxide: it bursts into flame
immediately.
2. The retention time of the main peak from nitrous oxide coincides with
that of nitrous oxide by gas chromatography.
Limit
Colour of the test solution is not deeper than the reference solutions
Analytical Method
Pass through acidified methyl red and bromothymol blue test solution in a
Nessler tube. Compare colour against control solution
Limit
Analytical Method
Pass through potassium permanganate solution in a Nessler tube.

Compare colour against control solution
Limit
Analytical Method
Pass through potassium iodide-starch solution in a Nessler tube. Compare

colour against control solution
Limit
Analytical Method

against control solution
Limit
Analytical Method

control solution of barium hydroxide containing sodium hydrogen carbonate
Limit
No peak observed at the same retention time as that for carbon monoxide
Analytical Method
Gas Chromatography
CO
CO2
Chloride
Oxidising
Reducing
Substances Substances
Acidity or
alkalinity
Purity
Assay
Assay
Specification
97.0 vol% of N2O .
Analytical Method
Gas chromatography
19
MGC
6.3
DOC 152/11
Carbon Dioxide
Carbon Dioxide
Monograph
JP
Name
Carbon Dioxide
Chemical Formula
CO2
Definition
Carbon Dioxide contains not less than 99.5 vol% of CO2
Description
Identification
Carbon Dioxide is a colourless, odourless gas at room temperature and

under atmospheric pressure.
1 Put a flaming splinter of wood into carbon dioxide and the flame is
extinguished immediately.
2. Pass carbon dioxide into calcium hydroxide and a white precipitate is
produced. Add acetic acid to the precipitate and it dissolves with
effervescence.
Limit
The test solution is not more coloured than the control solution.
Analytical Method
Pass through water in a Nessler tube and add methyl orange detector.
Compare colour against control solution.
Limit
The turbidity is the same as the control solution.
Analytical Method

against control solution.
Limit
No peak is observed at the same retention time as that for carbon

monoxide.
Analytical Method
Gas Chromatography.
Limit
The peak area of air in carbon dioxide by chromatography is less than that
of 0.5 % vol N2. No other peak appears.
Analytical Method
Gas Chromatography.
Oxygen &
Nitrogen
CO
Reducing
Substances*
Acidity
Purity
Assay
Assay
Specification
99.5 vol% of CO2.
Analytical Method
Volumetric Gas Absorption Apparatus
*
Reducing substances includes test for phosphine (PH3) hydrogen sulphide (H2S) and
reducing organic substances.
20
MGC
6.4
DOC 152/11
Nitrogen
Nitrogen
Monograph
JP
Name
Nitrogen
Chemical Formula
N2
Definition
Nitrogen contains not less than 99.5 vol% of N2
Description
Nitrogen is a colourless, odourless gas.
Identification
Put a burning wood splinter into nitrogen and the flame is extinguished
immediately.
CO2
Purity
Limit
Not specified (can be calculated by the method)
Analytical Method

control solution of barium hydroxide containing hydrogen carbonate
Assay
Assay
Specification
99.5 vol% of N2.
Analytical Method
Gas chromatography.
21

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MEDICAL GASES

EUROPEAN INDUSTRIAL GASES ASSOCIATION AISBL

JIMGA (Nippon Sanso Corp)

Scope and purpose .......................................................................................................................... 1

Specifications and test methods ...................................................................................................... 2

European Pharmacopoeia test requirements ........................................................................... 3

Currency of Information ................................................................................................................... 4

Comparison tables ........................................................................................................................... 4

Medical Oxygen ........................................................................................................................ 5

Japanese Pharmacopoeia ............................................................................................................. 18

Medical Oxygen ...................................................................................................................... 18

Scope and purpose

European Pharmacopoeia (Ph Eur)

Specifications and test methods

Low Oxygen Nitrogen

Synthetic Medicinal Air

assay of the product;

approved analytical method for identifying the gas;

approved analytical method for determining the assay, and

European Pharmacopoeia test requirements

Gas Detector Tubes

Chromatographic Separation Techniques

Carbon Dioxide in Gases

Carbon Monoxide in Gases

Nitrogen Monoxide and Nitrogen Dioxide in Gases

7.0 (July 2010)

Oxygen contains not less than

Oxygen contains not less than

Volumetric Gas Absorption

300 ppm V/V

300 ppm V/V

No Tests Section specified

90.0% O2 96.0% V/V O2

90.0% O2 96.0% V/V O2

Volumetric Gas Absorption

300 ppm V/V

No specific Tests Section

98.0% V/V N2O

1.0% air indicating

300 ppm V/V

300 ppm V/V

No specific Tests Section

1.0% O2 indicates 99.0% V/V of

300 ppm V/V

300 ppm V/V

No specific Tests Section

Nitrogen 97 Percent is Nitrogen

Extinguishing of burning wood

2.5 ppm V/V

Low Oxygen Nitrogen

Low Oxygen Nitrogen

Nitrogen Low Oxygen

This monograph applies to

Examine the chromatograms

Oxygen Analyser with

No Test Section specified

or - Glowing wood splinter

99.5% V/V CO2

99.0% V/V of CO2

No specific Tests Section

20.4%V/V O2 21.4 % V/V

19.5% V/V O2 23.5% V/V

500 ppm V/V

2 ppm V/V in total