In analytical sample preparation, extraction and leaching of chemical compounds from syringe filters are major concerns particularly when using Liquid

Chromatography/Mass Spectrometry (LCMS) for analysis. An underlying issue when filtration is used for sample preparation is the need to reduce the

amount of extractable and leachable compounds in the syringe filter effluents that may ultimately jeopardize analytical results and data interpretation.

Two common issues related to filtration for LCMS sample preparation are the presence of extraneous chromatographic peaks and ion suppression/

enhancement. The former could result in co-elution of extractable and leachable compounds with analytes of interest. The latter, also known as matrix

effects (ME), is of particular concern to LCMS users utilizing the most versatile and commonly used MS interface - Electrospray Ionization (ESI).

To address these concerns, Pall Corporation has developed a new Acrodisc® MS syringe filter, which is certified for low extractables using a highly

sensitive LCMS method. This syringe filter exhibits excellent compatibility and is made of high quality water-wettable polytetrafluoroethylene (WWPTFE)

membrane and high-density polyethylene (HDPE) housing materials.

The development of the Acrodisc MS syringe filters is presented in this study. In addition, the cleanliness of filter effluents using Pall’s Acrodisc MS syringe

filters and two commercially available alternative syringe filters were compared by evaluating the presence of extractable/leachable compounds in the

filter effluents under the same filtration and LC/ESI/MS analytical test conditions. Moreover, the ME (ion suppression/enhancement) due to potentially

interfering extractable/leachable compounds were studied for the analyses of three drug substances by comparing the MS signal intensity of each drug

substance spiked into the filter effluent against a control solution using fast gradient LC/ESI/MS.

Optimized Materials of Construction

Filter Media: WWPTFE membrane

Housing: Specially chosen HDPE

Key Properties (25 mm Discs)

Pore Size Rating: 0.2 µm

Effective Filtration Area: 3.9 cm2

Maximum Operating Pressure and Temperature: 60 psi at 21-24 ºC (70-75 °F),

30 psi at 55 ºC (131 °F)

Typical Water Flow Rate: 140 mL/min at 30 psi

Cleanliness: Verified by LCMS using an internal procedure

LCMS (ES+) Total Ion Current Chromatograms of Effluents Using Various Fluids

*System peak on each chromatogram

Filters were soaked in each solvent for 24 hours under ambient conditions.

Analyzed using UPLC/UV/MS method capable of detecting 50 ppb of various polymer additives.

UV data and ES(-) data (not presented) also showed cleanliness of the effluents.

Compatibility of Acrodisc MS SyringeFilters with Various Chemicals

Total of 51 chemicals were tested ( not all results are shown).

No visual defects (e.g. swelling, color change) and significant changes in bubble point after 48 hr. soak were observed.

LCMS AnalysisConditions: UPLC Gradient Method. Detection: ES(+)/MS. Mass Range: 100-1400 amu.

Column: ACQUITY� UPLC BEH C18, 1.7 µm (Waters Corporation), Mobile Phase: A (MeOH +

0.01% FA) and B (Water + 0.01% FA). FA – Formic Acid, MEOH - Methanol.

Test Fluids: Acetonitrile (ACN), 50:50 (v/v) ACN:Water, Methanol (MeOH), 50:50 (v/v)

MeOH:Water

Products Tested: Acrodisc MS Filters, Competitor A (PVDF Filters), Competitor B

(Hydrophilic PTFE Filters). Competitor products evaluated have low-extractable claims.

Total Ion Current Chromatograms of the Effluents

Competitor A filters are not compatible with ACN, and were therefore not

tested using this solvent.

Products Tested: Acrodisc MS syringe filters, Competitor A (PVDF filters), Competitor B

(hydrophilic PTFE filters). Competitor products evaluated have low extractable claims.

Matrix Effect (ME) was evaluated using the following equation:

% ME = Response in Filtered Solution

x 100 Response in Unfiltered Solution (Control)

where % ME = 100 - no matrix effect, > 100% ion enhancement and < 100% ion suppression

Matrix Effects Observed for Each Analyte

Note: Dashed lines (---) indicate no matrix effect (i.e. % ME = 100)

A new, unique syringe filter with broad chemical compatibility and low extractable/leachable materials has been developed for LCMS applications by Pall

Corporation. This study demonstrates that Acrodisc MS syringe filters are an excellent choice for LCMS sample preparation using aqueous, mild organic

solvents, and mixtures thereof.

Note: This work was completed using a 25 mm Acrodisc MS syringe filter. The product is also available in a 13 mm version suitable for samples as small

as 25 µL.

Development of Low Extractable Syringe Filters for Liquid Chromatography/Mass Spectrometry Applications

Gilbert E. Tumambac, Weibing Ding, and Larry Scheer; Pall Corporation, Ann Arbor, MI USA

ABSTRACT EFFLUENT CLEANLINESS UNDER VARIOUS CONDITIONS

PRODUCT DEVELOPMENT

© 2013, Pall Corporation. Pall, , and Acrodisc are trademarks of Pall Corporation. ® indicates a trademark registered in the USA. �ACQUITY UPLC is a trademark of

Waters Corporation. 2/13, GN13.8468

SUMMARY AND CONCLUSIONS

CLEANLINESS STUDIES

MembraneMaterials

Preselection Based on Physical and Chemical Properties

Extractables Analysis by LCMS

Optimized Product

Product Quali!cation Cleanliness and Matrix Effect Studies

HousingMaterials

CH2CI2

0.01N HCI

Acetonitrile

Methanol

Water

*

Acids

Alcohols

Bases

Esters

Ethers

Glycols

Hydrocarbons (HC)

Halogenated HCs

Oils

Ketones/Aldehydes

Others

VisualExam

Soak For 48 Hours Under Ambient Condiditon

Integrity Test by Bubble Point

Integrity Test by Bubble Point

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Chemical Name

Collect ~ 2 mL ef�uent

25 mm Syringe Filtersn = 10 per vendor

50:50 MeOH:Water MeOH 50:50 ACN:Water

ACN

OPTIMIZED PRODUCT

CHEMICAL COMPATIBILITY

CHEMICAL COMPATIBILITY MATRIX EFFECT STUDIES

Collect ~ 2 mL ef�uent

25 mm Syringe Filtersn = 25 per vendor

MeOH

Pool Samples

Mometasome Furoate

Verapamil

Acetaminophen

Analytes in Un!ltered MeOH

Conditions: Ballistic UPLC gradient method. Detection: selected ion recording (SIR), ES(+)/MS for MometasoneFuroate and Verapamil, ES(-)/MS for Acetaminophen. Column:ACQUITY UPLC BEH C18, 1.7 µm), Mobile phase: A (MeOH +0.01% FA) and B (Water + 0.01% FA).

COMPETITOR B

COMPETITOR A

PALL

CONTROL

Inte

nsity

Mometasone Furoate

Verapamil

Acetaminophen

SIR Chromatogram Showing Ion Suppression at 1 PPMMometasone Furoate

Contact Phone: 800.521.1520 (USA and Canada) • (+)800.PALL.LIFE (Outside USA and Canada) • www.pall.com/lab • E-mail: LabSupport@pall.com