ASTM F2459-18

Standard Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis

SIGNIFICANCE AND USE
5.1 This test method is suitable for determination of the total amount of extractable residue in metallic medical components. Extractable residue includes aqueous and non-aqueous residue, as well as non-soluble residue.  
5.2 This test method recommends the use of a sonication technique to extract residue from the medical component. Other techniques, such as solvent reflux extraction, could be used but have been shown to be less efficient in some tests, as discussed in X1.2.  
5.3 This test method is not applicable for evaluating the extractable residue for the reuse of a single-use component (SUD).
SCOPE
1.1 This test method covers the quantitative assessment of the amount of residue obtained from metallic medical components when extracted with aqueous or organic solvents.  
1.2 This test method does not advocate an acceptable level of cleanliness. It identifies two techniques to quantify extractable residue on metallic medical components. In addition, it is recognized that this test method may not be the only method to determine and quantify extractables.  
1.3 Although these methods may give the investigator a means to compare the relative levels of component cleanliness, it is recognized that some forms of component residue may not be accounted for by these methods.  
1.4 The applicability of these general gravimetric methods have been demonstrated by many literature reports; however, the specific suitability for applications to all-metal medical components will be validated by an Interlaboratory Study (ILS) conducted according to Practice E691.  
1.5 This test method is not intended to evaluate the residue level in medical components that have been cleaned for reuse. This test method is also not intended to extract residue for use in biocompatibility testing.
Note 1: For extraction of samples intended for the biological evaluation of devices or materials, refer to ISO 10993–12.  
1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.7 This standard may involve hazardous or environmentally-restricted materials, operations, and equipment. This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.8 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.

General Information

• Status: Published
• Publication Date: 31-Jan-2018
• ICS: 11.100.99 - Other standards related to laboratory medicine
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.15 - Material Test Methods

Relations

• Replaces: ASTM F2459-12 - Standard Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis
• Effective Date: 01-Feb-2018
• Refers: ASTM G121-18 - Standard Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
• Effective Date: 01-Dec-2018
• Refers: ASTM G131-96(2016) - Standard Practice for Cleaning of Materials and Components by Ultrasonic Techniques
• Effective Date: 01-May-2016
• Refers: ASTM G136-03(2016) - Standard Practice for Determination of Soluble Residual Contaminants in Materials by Ultrasonic Extraction
• Effective Date: 01-May-2016
• Refers: ASTM E691-13 - Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method
• Effective Date: 01-May-2013
• Refers: ASTM E691-11 - Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method
• Effective Date: 01-Nov-2011
• Refers: ASTM G136-03(2009) - Standard Practice for Determination of Soluble Residual Contaminants in Materials by Ultrasonic Extraction
• Effective Date: 01-Apr-2009
• Refers: ASTM E691-08 - Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method
• Effective Date: 01-Oct-2008
• Refers: ASTM G131-96(2008) - Standard Practice for Cleaning of Materials and Components by Ultrasonic Techniques
• Effective Date: 01-Sep-2008
• Refers: ASTM E691-05 - Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method
• Effective Date: 01-Nov-2005
• Refers: ASTM G121-98(2015)e1 - Standard Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
• Effective Date: 01-Sep-2004
• Refers: ASTM G121-98(2010)e1 - Standard Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
• Effective Date: 01-Sep-2004
• Refers: ASTM G136-03 - Standard Practice for Determination of Soluble Residual Contaminants in Materials by Ultrasonic Extraction
• Effective Date: 10-Sep-2003
• Refers: ASTM E691-99 - Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method
• Effective Date: 10-May-1999
• Refers: ASTM G121-98(2004) - Standard Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
• Effective Date: 10-Sep-1998

Overview

ASTM F2459-18 is the standard test method established by ASTM International for extracting residue from metallic medical components and quantifying it via gravimetric analysis. This method provides a validated and reproducible approach to measure the total extractable residue-including aqueous, non-aqueous, and non-soluble fractions-from metallic medical devices. The cleanliness of medical components such as implants and single-use devices is critical to minimize potential adverse biological responses caused by surface contamination or manufacturing residues.

The standard details extraction and analysis procedures using either sonication or solvent reflux methods, which are broadly recognized in both regulatory and industrial settings for assessing the cleanliness of new metallic medical components.

Key Topics

• Extractable Residue Definition: The test covers the evaluation of residues that can be extracted from metallic surfaces using water or organic solvents. These residues include water-soluble contaminates (e.g., salts, surfactants), non-water soluble residues (oils, hydrocarbons), and non-soluble debris (metals, organics, ceramics).
• Extraction Techniques:
  • Sonication: The recommended method uses ultrasonic baths, which have demonstrated higher extraction efficiency for certain residues.
  • Solvent Reflux Extraction: Also included but noted as less efficient in some cases.
• Quantification: Gravimetric analysis enables quantifying the total residue mass extracted from the medical component.
• Applicability: Suitable for assessing new, unused metallic medical components only-not intended for evaluating devices cleaned for reuse or for biocompatibility extraction testing.
• Reporting: Results are reported as mass per surface area, mass per component, and corrected for extraction efficiency.

Applications

ASTM F2459-18 is widely applied in the medical device manufacturing industry to ensure metallic medical components-such as implants and devices intended for single use-meet stringent cleanliness standards. Typical use cases include:

• Quality Control in Manufacturing: Verifying that finished metallic medical products meet internal or regulatory cleanliness specifications.
• Process Validation: Assessing and optimizing manufacturing, cleaning, or surface preparation processes by quantifying residual contaminants.
• Comparative Cleanliness Studies: Comparing the effectiveness of different cleaning agents or methods for residue removal from metallic surfaces.
• Regulatory Compliance: Supporting documentation for FDA submissions or CE marking, demonstrating a validated protocol to quantify and control extractable residues.

The method is recognized for helping manufacturers minimize patient risk and ensure compliance with industry expectations for medical implant cleanliness.

Related Standards

ASTM F2459-18 references and complements several other important standards:

• ASTM E691: Practice for conducting interlaboratory studies to determine the precision of a test method.
• ASTM G121: Practice for preparation of contaminated test coupons to evaluate cleaning agents.
• ASTM G131 / G136: Practices for cleaning materials and determining residual contaminants by ultrasonic extraction.
• ISO 10993-12: Guidance for sample preparation and reference materials in the biological evaluation of medical devices (for biocompatibility testing).

Other relevant keywords and related topics include extractable residue, gravimetric quantification, metallic medical devices, ultrasonic cleaning, solvent extraction, and contamination control.

---

By following ASTM F2459-18, manufacturers can quantitatively assess and compare the cleanliness of metallic medical components, ensuring the reliability and safety of devices intended for critical healthcare applications.

Standards Content (Sample)

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F2459 − 18
Standard Test Method for
Extracting Residue from Metallic Medical Components and
Quantifying via Gravimetric Analysis
This standard is issued under the fixed designation F2459; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.8 This international standard was developed in accor-
dance with internationally recognized principles on standard-
1.1 This test method covers the quantitative assessment of
ization established in the Decision on Principles for the
the amount of residue obtained from metallic medical compo-
Development of International Standards, Guides and Recom-
nents when extracted with aqueous or organic solvents.
mendations issued by the World Trade Organization Technical
1.2 This test method does not advocate an acceptable level
Barriers to Trade (TBT) Committee.
of cleanliness. It identifies two techniques to quantify extract-
able residue on metallic medical components. In addition, it is
2. Referenced Documents
recognized that this test method may not be the only method to
2.1 ASTM Standards:
determine and quantify extractables.
E691 Practice for Conducting an Interlaboratory Study to
1.3 Although these methods may give the investigator a
Determine the Precision of a Test Method
means to compare the relative levels of component cleanliness,
G121 Practice for Preparation of Contaminated Test Cou-
it is recognized that some forms of component residue may not
pons for the Evaluation of Cleaning Agents
be accounted for by these methods.
G131 Practice for Cleaning of Materials and Components by
1.4 The applicability of these general gravimetric methods Ultrasonic Techniques
G136 Practice for Determination of Soluble Residual Con-
have been demonstrated by many literature reports; however,
taminants in Materials by Ultrasonic Extraction
the specific suitability for applications to all-metal medical
componentswillbevalidatedbyanInterlaboratoryStudy(ILS)
2.2 ISO Standard:
conducted according to Practice E691.
ISO 10993–12 Biological Evaluation—Sample Preparation
and Reference Materials
1.5 This test method is not intended to evaluate the residue
level in medical components that have been cleaned for reuse.
3. Terminology
This test method is also not intended to extract residue for use
in biocompatibility testing.
3.1 Definitions:
3.1.1 ionic compounds/water soluble residue—residue that
NOTE 1—For extraction of samples intended for the biological evalu-
ation of devices or materials, refer to ISO 10993–12. is soluble in water, including surfactants and salts.
1.6 The values stated in SI units are to be regarded as 3.1.2 non-soluble debris—residue including metals, organic
standard. No other units of measurement are included in this solids, inorganic solids, and ceramics.
standard.
3.1.3 non-water soluble residue—residuesolubleinsolvents
1.7 This standard may involve hazardous or other than water. Inclusive in this are oils, greases,
environmentally-restricted materials, operations, and equip- hydrocarbons, and low molecular weight polymers. Typical
solvents used to dissolve these residues include chlorinated or
ment. This standard does not purport to address all of the
safety concerns, if any, associated with its use. It is the fluorinated solvents, or low molecular weight hydrocarbons.
responsibility of the user of this standard to establish appro-
3.1.4 reflux system—an apparatus containing an extraction
priate safety, health, and environmental practices and deter-
vessel and a solvent return system. It is designed to allow
mine the applicability of regulatory limitations prior to use.
1 2
This test method is under the jurisdiction ofASTM Committee F04 on Medical For referenced ASTM standards, visit the ASTM website, www.astm.org, or
and Surgical Materials and Devices and is the direct responsibility of Subcommittee contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
F04.15 on Material Test Methods. Standards volume information, refer to the standard’s Document Summary page on
Current edition approved Feb. 1, 2018. Published March 2018. Originally the ASTM website.
approved in 2005. Last previous edition approved in 2012 as F2459 – 12. DOI: Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St.,
10.1520/F2459-18. 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2459 − 18
boiling of the solvent in the extraction vessel and to return any 6. Apparatus
vaporized solvent to the extraction vessel.
6.1 Ultrasonic Bath, for extraction. The bath must be large
3.1.5 reuse—the repeated or multiple use of any medical
enough to hold an extraction beaker containing the medical
component (whether labeled SUD or reusable) with reprocess- component. This apparatus is used with the technique de-
ing (cleaning, disinfection, or sterilization, or combination
scribed in 11.5. Alternatively, an ultrasonic probe can be used
thereof) between patient uses.
with a bath.
3.1.6 single use device (SUD)—adisposablecomponentthat
6.2 Solvent Reflux Extraction Assembly, shown in Fig. 1.
is intended to be used on one patient during a single procedure.
Thisassemblyiscomposedofavessellargeenoughtoholdthe
medical component, and a water-cooled refluxing column. A
3.1.7 surface area—theprojectedsurfaceareaofapart.This
heating manifold or hotplate stirrer capable of reaching the
area does not include the internal porosity of parts with
boiling point of the solvent is also included. This apparatus is
cancellous, porous, or wire structure.
used in the procedure described in 11.3.ASoxhlet extractor, as
3.2 Symbols:
shown in Fig. 2, could be used as well using the procedure
described in 11.3.
m = weight of extraction vessel, foil, and component before
extraction
6.3 Analytical Balance, with 0.1 mg accuracy or better.
m = weight of extraction vessel, component, foil, and
6.4 Balance, with accuracy of 10 mg or better and sufficient
solvent after extraction
capacity to weigh the extraction beaker with the medical
m = mass of clean beaker and foil used to hold removed
component and solvent combined.
aliquot of extracted solution
m = mass of beaker, foil, and aliquot of solution before
6.5 Glass Beaker and Extraction Vessel, large enough to
drying
hold sufficient solvent to cover the medical component in the
m = mass of beaker, foil, and residue after evaporating
5 extraction vessel. Additionally, metal beakers could be used.
solvent
Plastic beakers should not be used as low molecular weight
m = mass of new filter
6 residues could be extracted from the beakers.
m = mass of filter following filtration and drying
6.6 Desiccator.
m = mass of pre-dried sample specimen prior to extraction
m = mass of pre-dried sample specimen after extraction
9 6.7 Pipets, for transferring liquid. Some solvents can leach
m = mass of residue in removed aliquot
a
extractable compounds from plastic pipets. Glass or metallic
c = concentration of residue in solution
r
pipets are recommended for organic solvents.
c = concentration of residue in blank solutions
b
6.8 Aluminum Foil, degreased in extraction solvent.
m = mass of soluble residue in the overall extract, corrected
r
for the blank runs
6.9 Forceps, Tweezers, or Tongs, cleaned with acetone or
m = weight of insoluble debris
i
extraction solvent.
m = mass of soluble and insoluble residue
t
6.10 Filtration Apparatus, containing a removable 0.2 µm
E = extraction efficiency
filter medium that is non-soluble in the extraction solvent.
4. Summary of Test Method
6.11 Non-Corrosive (Glass or Non-Corrosive Metal) Trays.
4.1 This test method describes the extraction and quantita-
6.12 Laboratory Oven or rotary evaporator.
tive analysis procedures used to detect and quantify the total
amount of extractable residue from metallic medical compo-
7. Reagents and Materials
nents. The residues are grouped into three categories: (1)
7.1 Each user needs to demonstrate solubility of all of their
water-soluble extractables; (2) non-water soluble extractables;
suspect sources of residue in the solvent(s) of choice. Several
and (3) non-soluble debris.
solvents may be required if more than one type of residue may
be present on the component. The selected solvent shall not
5. Significance and Use
dissolve or change the implant material.
5.1 Thistestmethodissuitablefordeterminationofthetotal
7.2 Spectroscopy or ACS-grade solvents should be used.
amount of extractable residue in metallic medical components.
Extractable residue includes aqueous and non-aqueous residue, 7.3 High purity, deionized, or equivalent water should be
as well as non-soluble residue. used.
5.2 This test method recommends the use of a sonication
8. Hazards
technique to extract residue from the medical component.
Other techniques, such as solvent reflux extraction, could be 8.1 Many organic solvents are toxic, flammable, or explo-
used but have been shown to be less efficient in some tests, as
sive and should be handled only with chemically protective
discussed in X1.2. laboratory gloves and used in a fume hood.
5.3 This test method is not applicable for evaluating the 8.2 If sonication is used, the user should make sure that the
extractable residue for the reuse of a single-use component solvent is not heated, directly or through sonication, to a
(SUD). temperature above the flash point of the solvent.
F2459 − 18
FIG. 1 Sample Solvent Reflux Extractor Assembly
9. Sampling, Test Specimens, and Test Units pre-cleaned medical components with known amounts of the
target residue, then extracting and quantifying the target
9.1 Metallicmedicalcomponentsshouldbetakeninrandom
residue. When using this method, the extraction efficiency E is
groupings from different lots if available.
the ratio of the amount of recovered residue to the doped
9.2 It is up to the user to determine the number of medical
amount of residue. Recovery efficiency may also be deter-
components that need to be used to establish known reproduc-
mined by exhaustive extraction. The exhaustive extraction
ibility.
technique uses medical components which have not been
cleaned and contain unknown amounts of the target residue(s).
9.3 Itisuptotheusertodeterminethenumberoftestblanks
that need to be used to establish known reproducibility. These components should be extracted using the selected
extraction technique until no significant increase in the cumu-
9.4 Separate components should be tested for organic and
lative residue level is detected upon re-extraction, or until the
aqueous extractions.
incremental amount extracted is less than 10 % of what was
9.5 If a long medical component is cut, it is recommended
detected in the first extraction. When using this approach, the
that the original length and the cut lengths be recorded before
extraction efficiency E is the ratio of the amount of recovered
the final cleaning operation for validation purposes. Individual
residue from the first extraction to the total amount of
cut lengths may be separately extracted and the results com-
recovered residue from all extractions performed.
bined to provide a total residue value for the medical compo-
10.3 The user should adjust the extraction parameters in
nent. Cutting lubricants must be avoided in this procedure.
11.3.11, 11.5.8,or 11.7.12, and/or select the appropriate
solvent, in order to achieve an extraction efficiency of E >
10. Limits of Detection and Recovery Efficiency
75 %. This step should be performed if target residues are
10.1 Standardized test coupons can be prepared according
known a priori. In the case of mixed residues, extraction
to Practice G121. Limits of detection for the two extraction
efficiency may not be able to be determined and the exhaustive
techniques described in Section 11 can be assessed by placing
extraction of the test specimen may be performed.
known amounts of residues on the test coupons, and perform-
ing the extraction and analyses described in Section 11.
11. Procedure
10.2 Recovery Effıciency—The recovery efficiency of the 11.1 If more than one specimen is to be extracted
selected extraction technique can be determined by doping collectively, record the number of specimens.
F2459 − 18
FIG. 2 Sample Soxhlet Extractor Assembly
11.2 If multiple specimens are to be extracted collectively, 11.3.8 Charge the flask with enough solvent to completely
they must be of the same type and size. cover the component(s) and assemble the reflux system.
11.3.9 Start flow of cooling water through the condenser.
11.3 Reflux Extraction by Extract Mass:
11.3.10 Adjust the hotplate stirrer or heating manifold to
11.3.1 Equipmentmayneedtobecleanedwithnitricacidor
maintain the solvent at a brisk boil with moderate constant
other appropriate means prior to solvent cleaning.
stirring.
11.3.2 Clean the extraction equipment by rinsing at least
11.3.11 Extract the component(s) for 4 h or for approxi-
three times with spectroscopy-grade hexane or another suitable
mately 10 cycles if using a Soxhlet extractor, or the amount of
solvent. The extraction solvent may be used.
time needed to achieve an extraction efficiency greater than 75
11.3.3 Air or oven dry all beakers and glassware at room
%. The extraction time or number of cycles can be adjusted by
temperature in a fume hood and store in a dessicator prior to
the user based on internal. The extraction time or number of
use.
cycles can be adjusted by the user based on internal validation
11.3.4 Assemble the extraction apparatus as shown in Fig.
of their target residue.
1.
11.3.12 After the extraction period is complete, turn off the
11.3.5 Do not use any type of joint grease on the extraction
hot plate and allow the system to cool. Carefully open the
assembly. It can dissolve in the solvent and contaminate the
apparatus. If a Soxhlet extractor is used, heavy debris may stay
solution.Polytetrafluoroethylene(PTFE)sleevesortapecanbe
inthetoppartoftheextractor.Thisdebriscanbewasheddown
used to seal the joints if necessary.
into the collection vessel with fresh extraction solvent.
11.3.6 Place the sample component in the extractor vessel
11.3.13 Weigh the extraction vessel, component, and
and add a magnetic stirring bar or PTFE boiling stones to
reducethepotentialforboilingretardationinthesystemduring solvent, and record the weight as m .
reflux. The stir bar or boiling stones, or both, should be 11.3.14 Weigh an aliquot beaker large enough to hold an
carefully cleaned in a suitable solvent prior to use. aliquot of the extraction vessel along with a clean piece of foil
11.3.7 Weigh the extractor vessel with the component on a and record the weight as m . The beaker should be weighed to
balance and record the weight, m . a resolution of at least 0.1 mg.
F2459 − 18
11.3.15 Allow the insoluble debris to settle in the extraction carefulnottowithdrawanyinsolubledebrisfromthebottomof
vessel for 1 h. Withdraw an aliquot of the extracted solution the extraction vessel. Weigh the solution with beaker and foil
that comprises at least 90 % of the total extracted solution and and record as m .
place in the aliquot beaker as described in 11.3.14, being 11.5.11.1 Allow the solvent to completely evaporate in a
carefulnottowithdrawanyinsolubledebrisfromthebottomof
fume hood at room temperature. See X1.1.3 for more details.
the extraction vessel. Weigh the solution with beaker and foil
11.5.11.2 Place the beaker, with residue, in a dessicator for
and record as m .
a minimum of 2 h.
11.3.15.1 Allow the solvent to completely evaporate in a
11.5.11.3 Weigh the beaker with foil and residue and record
fume hood at room temperature or with moderate warming.
as m .
See X1.1.3 for more details.
11.5.11.4 If the volume of the aliquot beaker is smaller than
11.3.15.2 Place the beaker, with residue, in a dessicator for
the aliquot, multiple aliquots can be removed from the extrac-
a minimum of 2 h.
tion vessel, weighing each aliquot, evaporating the solvent and
11.3.15.3 Weigh the beaker and foil again and record as m .
5 collecting the next aliquot. The solution weight m is the sum
11.3.15.4 If the volume of the aliquot beaker is smaller than
of the aliquot weights. The final beaker weight m should be
the aliquot, multiple aliquots can be removed from the extrac-
recorded as described in 11.5.11.3.
tionvessel,weighingeachaliquot,e
...

This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F2459 − 12 F2459 − 18
Standard Test Method for
Extracting Residue from Metallic Medical Components and
Quantifying via Gravimetric Analysis
This standard is issued under the fixed designation F2459; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 This test method covers the quantitative assessment of the amount of residue obtained from metallic medical components
when extracted with aqueous or organic solvents.
1.2 This test method does not advocate an acceptable level of cleanliness. It identifies one techniquetwo techniques to quantify
extractable residue on metallic medical components. In addition, it is recognized that this test method may not be the only method
to determine and quantify extractables.
1.3 Although these methods may give the investigator a means to compare the relative levels of component cleanliness, it is
recognized that some forms of component residue may not be accounted for by these methods.
1.4 The applicability of these general gravimetric methods have been demonstrated by many literature reports; however, the
specific suitability for applications to all-metal medical components will be validated by an Interlaboratory Study (ILS) conducted
according to Practice E691.
1.5 This test method is not intended to evaluate the residue level in medical components that have been cleaned for reuse. This
test method is also not intended to extract residue for use in biocompatibility testing.
NOTE 1—For extraction of samples intended for the biological evaluation of devices or materials, refer to ISO 10993–12.
1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.7 This standard may involve hazardous or environmentally-restricted materials, operations, and equipment. This standard
does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this
standard to establish appropriate safety safety, health, and healthenvironmental practices and determine the applicability of
regulatory limitations prior to use.
1.8 This international standard was developed in accordance with internationally recognized principles on standardization
established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued
by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
2. Referenced Documents
2.1 ASTM Standards:
E691 Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method
G121 Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
G131 Practice for Cleaning of Materials and Components by Ultrasonic Techniques
G136 Practice for Determination of Soluble Residual Contaminants in Materials by Ultrasonic Extraction
2.2 ISO Standard:
ISO 10993–12 Biological Evaluation—Sample Preparation and Reference Materials
3. Terminology
3.1 Definitions:
3.1.1 ionic compounds/water soluble residue—residue that is soluble in water, including surfactants and salts.
This test method is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.15 on Material Test Methods.
Current edition approved March 1, 2012Feb. 1, 2018. Published March 2012 March 2018. Originally approved in 2005. Last previous edition approved in 20052012 as
F2459 – 05.F2459 – 12. DOI: 10.1520/F2459-12.10.1520/F2459-18.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2459 − 18
3.1.2 non-soluble debris—residue including metals, organic solids, inorganic solids, and ceramics.
3.1.3 non-water soluble residue—residue soluble in solvents other than water. Inclusive in this are oils, greases, hydrocarbons,
and low molecular weight polymers. Typical solvents used to dissolve these residues include chlorinated or fluorinated solvents,
or low molecular weight hydrocarbons.
3.1.4 reflux system—an apparatus containing an extraction vessel and a solvent return system. It is designed to allow boiling of
the solvent in the extraction vessel and to return any vaporized solvent to the extraction vessel.
3.1.5 reuse—the repeated or multiple use of any medical component (whether labeled SUD or reusable) with reprocessing
(cleaning, disinfection, or sterilization, or combination thereof) between patient uses.
3.1.6 single use componentdevice (SUD)—a disposable component; component that is intended to be used on one patient during
a single procedure.
3.1.7 surface area—the projected surface area of a part. This area does not include the internal porosity of parts with cancellous,
porous, or wire structure.
3.2 Symbols:
m = weight of extraction vessel and component before extraction
m = weight of extraction vessel, foil, and component before extraction
m = weight of extraction vessel, component, foil, and solvent after extraction
m = mass of clean beaker and foil used to hold removed aliquot of extracted solution
m = mass of beaker, foil, and aliquot of solution before drying
m = mass of beaker, foil, and residue after evaporating solvent
m = mass of new filter
m = mass of filter following filtration and drying
m = mass of pre-dried sample specimen prior to extraction
m = mass of pre-dried sample specimen after extraction
m = mass of residue in removed aliquot
a
c = concentration of residue in solution
r
c = concentration of residue in blank solutions
b
m = mass of soluble residue in the overall extract, corrected for the blank runs
r
m = weight of insoluble debris
i
m = mass of soluble and insoluble residue
t
E = extraction efficiency
4. Summary of Test Method
4.1 This test method describes the extraction and quantitative analysis procedures used to detect and quantify the total amount
of extractable residue from metallic medical components. The residues are grouped into three categories: (1) water-soluble
extractables; (2) non-water soluble extractables; and (3) non-soluble debris.
5. Significance and Use
5.1 This test method is suitable for determination of the total amount of extractable residue in metallic medical components.
Extractable residue includes aqueous and non-aqueous residue, as well as non-soluble residue.
5.2 This test method recommends the use of a sonication technique to extract residue from the medical component. Other
techniques, such as solvent reflux extraction, could be used but have been shown to be less efficient in some tests, as discussed
in X1.2.
5.3 This test method is not applicable for evaluating the extractable residue for the reuse of a single-use component (SUD).
6. Apparatus
6.1 Ultrasonic Bath, for extraction. The bath must be large enough to hold an extraction beaker containing the medical
component. This apparatus is used with the technique described in 11.5. Alternatively, an ultrasonic probe can be used with a bath.
6.2 Solvent Reflux Extraction Assembly, shown in Fig. 1. This assembly is composed of a vessel large enough to hold the
medical component, and a water-cooled refluxing column. A heating manifold or hotplate stirrer capable of reaching the boiling
point of the solvent is also included. This apparatus is used in the procedure described in 11.3. A Soxhlet extractor, as shown in
Fig. 2, could be used as well using the procedure described in 11.3.
6.3 Analytical Balance, with 0.1 mg accuracy or better.
6.4 Balance, with accuracy of 10 mg ofor better and sufficient capacity to weigh the extraction beaker with the medical
component and solvent combined.
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FIG. 1 Sample Solvent Reflux Extractor Assembly
6.5 Glass Beaker and Extraction Vessel, large enough to hold sufficient solvent to cover the medical component in the extraction
vessel. Additionally, metal beakers could be used. Plastic beakers should not be used as low molecular weight residues could be
extracted from the beakers.
6.6 Desiccator.
6.7 Pipets, for transferring liquid. Some solvents can leach extractable compounds from plastic pipets. Glass or metallic pipets
are recommended for organic solvents.
6.8 Aluminum Foil, degreased in extraction solvent.
6.9 Forceps, Tweezers, or Tongs, cleaned with acetone or extraction solvent.
6.10 Filtration Apparatus, containing a removable 0.2 μm filter medium that is non-soluble in the extraction solvent.
6.11 Non-Corrosive (Glass or Non-Corrosive Metal) Trays.
6.12 Laboratory Oven or rotary evaporator.
7. Reagents and Materials
7.1 Each user needs to demonstrate solubility of all of their suspect sources of residue in the solvent(s) of choice. Several
solvents may be required if more than one type of residue may be present on the component. The selected solvent shall not dissolve
or change the implant material.
7.2 Spectroscopy or ACS-grade solvents should be used.
7.3 High purity, deionized, or equivalent water should be used.
8. Hazards
8.1 Many organic solvents are toxic, flammable, or explosive and should be handled only with chemically protective laboratory
gloves and used in a fume hood.
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FIG. 2 Sample Soxhlet Extractor Assembly
8.2 If sonication is used, the user should make sure that the solvent is not heated, directly or through sonication, to a temperature
above the flash point of the solvent.
9. Sampling, Test Specimens, and Test Units
9.1 Metallic medical components should be taken in random groupings from different lots if available.
9.2 It is up to the user to determine the number of medical components that need to be used to establish known reproducibility.
9.3 It is up to the user to determine the number of test blanks that need to be used to establish known reproducibility.
9.4 Separate components should be tested for organic and aqueous extractions.
9.5 If a long medical component is cut, it is recommended that the original length and the cut lengths be recorded before the
final cleaning operation for validation purposes. Individual cut lengths may be separately extracted and the results combined to
provide a total residue value for the medical component. Cutting lubricants must be avoided in this procedure.
10. Limits of Detection and Recovery Efficiency
10.1 Standardized test coupons can be prepared according to Practice G121. Limits of detection for the two extraction
techniques described in Section 11 can be assessed by placing known amounts of residues on the test coupons, and performing the
extraction and analyses described in Section 11.
10.2 Recovery Effıciency—The recovery efficiency of the selected extraction technique can be determined by doping pre-cleaned
medical components with known amounts of the target residue, then extracting and quantifying the target residue. When using this
method, the extraction efficiency E is the ratio of the amount of recovered residue to the doped amount of residue. Recovery
efficiency may also be determined by exhaustive extraction. The exhaustive extraction technique uses medical components which
have not been cleaned and contain unknown amounts of the target residue(s). These components should be extracted using the
selected extraction technique until no significant increase in the cumulative residue level is detected upon re-extraction, or until
the incremental amount extracted is less than 10 % of what was detected in the first extraction. When using this approach, the
extraction efficiency E is the ratio of the amount of recovered residue from the first extraction to the total amount of recovered
residue from all extractions performed.
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10.3 The user should adjust the extraction parameters in 11.3.11 or , 11.5.8, or 11.7.12, and/or select the appropriate solvent,
or both, in order to achieve an extraction efficiency of E > 75 %. This step should be performed if target residues are known a priori.
In the case of mixed residues, extraction efficiency may not be able to be determined.determined and the exhaustive extraction of
the test specimen may be performed.
11. Procedure
11.1 If more than one specimen is to be extracted collectively, record the number of specimens.
11.2 If multiple specimens are to be extracted collectively, they must be of the same type and size.
11.3 Reflux Extraction: Extraction by Extract Mass:
11.3.1 Equipment may need to be cleaned with nitric acid or other appropriate means prior to solvent cleaning.
11.3.2 Clean the extraction equipment by rinsing at least three times with spectroscopy-grade hexane or another suitable solvent.
The extraction solvent may be used.
11.3.3 Air or oven dry all beakers and glassware at room temperature in a fume hood and store in a dessicator prior to use.
11.3.4 Assemble the extraction apparatus as shown in Fig. 1.
11.3.5 Do not use any type of joint grease on the extraction assembly. It can dissolve in the solvent and contaminate the solution.
Polytetrafluoroethylene (PTFE) sleeves or tape can be used to seal the joints if necessary.
11.3.6 Place the sample component in the extractor vessel and add a magnetic stirring bar or PTFE boiling stones to reduce the
potential for boiling retardation in the system during reflux. The stir bar or boiling stones, or both, should be carefully cleaned in
a suitable solvent prior to use.
11.3.7 Weigh the extractor vessel with the component on a balance and record the weight, m .
11.3.8 Charge the flask with enough solvent to completely cover the component(s) and assemble the reflux system.
11.3.9 Start flow of cooling water through the condenser.
11.3.10 Adjust the hotplate stirrer or heating manifold to maintain the solvent at a brisk boil with moderate constant stirring.
11.3.11 Extract the component(s) for 4 h or for approximately 10 cycles if using a Soxhlet extractor. extractor, or the amount
of time needed to achieve an extraction efficiency greater than 75 %. The extraction time or number of cycles can be adjusted by
the user based on internal. The extraction time or number of cycles can be adjusted by the user based on internal validation of their
target residue.
11.3.12 After the extraction period is complete, turn off the hot plate and allow the system to cool. Carefully open the apparatus.
If a Soxhlet extractor is used, heavy debris may stay in the top part of the extractor. This debris can be washed down into the
collection vessel with fresh extraction solvent.
11.3.13 Weigh the extraction vessel, component, and solvent, and record the weight as m .
11.3.14 Weigh an aliquot beaker large enough to hold an aliquot of the extraction vessel along with a clean piece of foil and
record the weight as m . The beaker should be weighed to a resolution of at least 0.1 mg.
11.3.15 Allow the insoluble debris to settle in the extraction vessel for 1 h. Withdraw an aliquot of the extracted solution that
comprises at least 90 % of the total extracted solution and place in the aliquot beaker as described in 11.3.14, being careful not
to withdraw any insoluble debris from the bottom of the extraction vessel. Weigh the solution with beaker and foil and record as
m .
11.3.15.1 Allow the solvent to completely evaporate in a fume hood at room temperature. temperature or with moderate
warming. See X1.1.3 for more details.
11.3.15.2 Place the beaker, with residue, in a dessicator for a minimum of 2 h.
11.3.15.3 Weigh the beaker and foil again and record as m .
11.3.15.4 If the volume of the aliquot beaker is smaller than the aliquot, multiple aliquots can be removed from the extraction
vessel, weighing each aliquot, evaporating the solvent, and collecting the next aliquot. The solution weight m is the sum of the
aliquot weights plus the foil weight. The final beaker weight m should be recorded as described in 11.3.15.3.
11.4 Blank Run:
11.4.1 Conduct test blank(s) using the same amount of solvent and rinses, but no component, for the complete extraction and
analysis procedure. Record all weights as above.
11.5 Sonication Extraction: Extraction by Extract Mass:
11.5.1 Background information on sonication extraction can be found in Practices G131 and G136.
11.5.2 Glassware may need to be cleaned with nitric acid or other appropriate means prior to solvent cleaning.
11.5.3 Clean the glassware by rinsing at least three times with spectroscopy-grad
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