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
CHEMICAL COMPATIBILITY
Compatibility of Acrodisc MS SyringeFilters with Various Chemicals
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).
% Change in Bubble Point
0.01N HCI
*
Acetonitrile
Methanol
Water
Verapamil
40
Mometasome Furoate
Acetaminophen
20
Pool Samples
Conditions: Ballistic UPLC gradient method. Detection:
selected ion recording (SIR), ES(+)/MS for Mometasone
Furoate 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).
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Collect ~ 2 mL effluent
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PRODUCT DEVELOPMENT
LCMS (ES+) Total Ion Current Chromatograms of Effluents Using Various Fluids
*System peak on each chromatogram
Housing
Materials
Analytes in Unfiltered MeOH
25 mm Syringe Filters
n = 25 per vendor
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.
Membrane
Materials
MeOH
60
CH2CI2
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.
MATRIX EFFECT STUDIES
d
Filters were soaked in each solvent for 24 hours under ambient conditions.
Total of 51 chemicals were tested ( not all results are shown).
Analyzed using UPLC/UV/MS method capable of detecting 50 ppb of various polymer additives.
No visual defects (e.g. swelling, color change) and significant changes in bubble point after 48 hr. soak were observed.
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:
Response in Filtered Solution
% ME =
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
UV data and ES(-) data (not presented) also showed cleanliness of the effluents.
Mometasone Furoate
Preselection Based on Physical
and Chemical Properties
CLEANLINESS STUDIES
CHEMICAL COMPATIBILITY
LCMS Analysis
Extractables Analysis by LCMS
Conditions: 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.
Acids
Alcohols
Bases
Integrity Test
by Bubble Point
Product Qualification
Cleanliness and
Matrix Effect Studies
Esters
Ethers
CONTROL
25 mm Syringe Filters
n = 10 per vendor
Visual
Exam
Test Fluids: Acetonitrile (ACN), 50:50 (v/v) ACN:Water, Methanol (MeOH), 50:50 (v/v)
MeOH:Water
Integrity Test
by Bubble Point
Products Tested: Acrodisc MS Filters, Competitor A (PVDF Filters), Competitor B
(Hydrophilic PTFE Filters). Competitor products evaluated have low-extractable claims.
Glycols
COMPETITOR A
Ketones/Aldehydes
COMPETITOR B
Total Ion Current Chromatograms of the Effluents
Oils
50:50 MeOH:Water
MeOH
Acetaminophen
50:50 ACN:Water
SIR Chromatogram Showing Ion Suppression at 1 PPM
Mometasone Furoate
{
Others
Optimized Materials of Construction
Verapamil
Collect ~ 2 mL effluent
Hydrocarbons (HC)
Halogenated HCs
OPTIMIZED PRODUCT
PALL
Intensity
Optimized Product
Filter Media: WWPTFE membrane
Housing: Specially chosen HDPE
Soak For 48 Hours Under Ambient Condiditon
Key Properties (25 mm Discs)
Note: Dashed lines (---) indicate no matrix effect (i.e. % ME = 100)
Pore Size Rating: 0.2 µm
ACN
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
SUMMARY AND CONCLUSIONS
Competitor A filters are not compatible with ACN, and were therefore not
tested using this solvent.
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.
Contact Phone: 800.521.1520 (USA and Canada) • (+)800.PALL.LIFE (Outside USA and Canada) • www.pall.com/lab • E-mail: LabSupport@pall.com
© 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