Quantitative PFAS Analysis in Medical Devices Using Triple Quadrupole LC/MS

Importance of the topic

Per‑ and polyfluoroalkyl substances (PFAS) are increasingly scrutinized in medical devices due to their persistence, potential health impacts, and widespread historic use for improving material properties (chemical stability, low friction, biocompatibility). Reliable, low‑level quantification of PFAS in device materials is essential for raw‑material qualification, finished‑product release, regulatory compliance, and life‑cycle stewardship as regulations (EPA, REACH and others) expand their scope.

Objectives and study overview

This application note describes an end‑to‑end analytical workflow developed to screen and quantify 73 native PFAS in representative medical device matrices (intravenous tubing, blood collection tubes, syringes). Goals were to (1) minimize system and procedural PFAS background, (2) provide sensitive quantification at low µg/kg levels in matrix, (3) demonstrate robust recovery and reproducibility across a broad chemical class, and (4) illustrate applicability to real samples.

Methodology

Sample preparation:

• Cut device material into small pieces (<1 cm2); weigh 1.00 ± 0.01 g into polypropylene tubes.
• Add 10 mL methanol; sonicate 1 hour at 60 °C (heat‑ and ultrasound‑assisted extraction, HUA).
• Shake 10–15 min at 1,500 rpm; centrifuge 5 min at 4,200 rpm.
• Filter supernatant through nylon syringe filter into LC vial; a 10‑fold dilution effectively occurs during processing.

Standards and calibration:

• 73 target PFAS, 34 extracted surrogate standards, and 3 non‑extracted internal standards; standards prepared in methanol at 0.01–50 µg/L with surrogates/ISTDs at 1 µg/L.
• Calibration acceptance: linearity across ≥5 levels with R2 > 0.992 for all targets; LOQs defined by matrix‑spike QC meeting 65–135% recovery plus identification criteria (S/N and ion‑ratio).

Chromatography and MS conditions (summary): gradient UHPLC separation on a ZORBAX RRHD Eclipse Plus C18 (2.1 × 100 mm, 1.8 µm) using 5 mM ammonium acetate (A) and MeOH (B) in a 14.5 min run. Feed Injection large‑volume method used 30 µL injection in 100% MeOH with adaptive feed speed (10% of pump flow) to maintain peak shape for early and late eluters. MS operated in negative electrospray with MRM on a triple quadrupole platform.

Used Instrumentation

Key instrumentation and configuration used in the workflow:

• Agilent 1290 Infinity III UHPLC system configured for PFAS analysis (purpose‑built to reduce fluorinated flow‑path components), including High‑Speed Pump and 1290 Infinity III Hybrid Multisampler enabling large‑volume Feed Injection.
• Analytical column: Agilent ZORBAX RRHD Eclipse Plus C18, 2.1 × 100 mm, 1.8 µm (95 Å).
• Guard column: ZORBAX RRHD Eclipse Plus C18 UHPLC guard, 2.1 mm, 1.8 µm.
• Mass spectrometer: Agilent 6475 LC/TQ operated in negative AJS‑ESI with unit Q1/Q3 resolution, 580 ms cycle time; typical source settings (gas temp 230 °C, sheath gas temp 375 °C, capillary −2,500 V).
• Consumables and solvents: LC/MS‑grade MeOH, ACN, IPA, ammonium acetate; PFAS‑suitable consumables verified per supplier guidance.

Main results and discussion

Background and sensitivity:

• Procedural blank signals were negligible, demonstrating the PFAS‑ready UHPLC/TQ configuration successfully minimized instrument and consumable contributions to background and allowed ultra‑trace analysis.
• Feed Injection optimization identified 30 µL at adaptive 10% feed speed as best compromise for peak shape and sensitivity across early and late eluting PFAS species.

Quantitative performance:

• Linearity: R2 > 0.992 for all 73 analytes (representative curves shown for PFOA, PFNA, PFOS, PFHxS).
• Limits of quantification: 65 of 73 targets achieved LOQs at 1 µg/kg in matrix, including all 40 mandatory PFAS from EPA Method 1633; several analytes required higher LOQs (examples at 10 or 100 µg/kg) or LLOQ in solvent for particularly problematic perfluorinated phosphinic acids due to recovery issues.
• Recovery: >87% of analytes had recoveries within the 65–135% acceptance range across low, medium, and high matrix‑spike QCs.
• Reproducibility: all targets exhibited %RSD ≤ 20% across QC levels; representative subset showed %RSD ≤ 13% at each level.

Application to real samples:

• Quality control sample: intravenous tubing used to benchmark method performance.
• Unknowns: blood collection tubes and medical syringes analyzed; trace PFOA was observed above method detection limits in both sample types, demonstrating method applicability for routine screening.

Benefits and practical applications

The workflow provides a practical, sensitive platform for PFAS monitoring in medical device materials with the following advantages:

• Low instrument and procedural background enabling ultratrace detection in matrix.
• Broad analyte coverage (73 native PFAS) including regulatory priority compounds (EPA 1633 list).
• Robust, simple methanol‑based HUA extraction compatible with common polymer matrices and amenable to routine QC labs.
• High reproducibility and acceptable recovery for the majority of targets, supporting quantitative surveillance during material selection, supplier qualification, and finished‑product testing.

Future trends and potential applications

Key directions to expand analytical capability and regulatory readiness include:

• Broader adoption of PFAS‑ready LC/TQ and validated consumables to standardize low‑background workflows.
• Integration of high‑resolution accurate‑mass (HRAM) screening for unknown and transformation products alongside targeted MRM panels.
• Automation and miniaturization of extraction workflows to increase throughput and reduce solvent use.
• Harmonization of reporting limits, LOQ definitions, and method validation criteria across regulatory frameworks to enable comparability between laboratories.
• Expansion of targeted panels and development of certified reference materials for medical device matrices to improve interlaboratory comparability.

Conclusion

The presented UHPLC–triple quadrupole workflow achieves ultralow PFAS background, high sensitivity, and robust quantitation for a broad PFAS panel in common medical device materials. With simple methanol HUA extraction, large‑volume Feed Injection, and MRM quantification on a PFAS‑ready LC/TQ platform, the method supports routine monitoring, supplier control, and regulatory compliance efforts while remaining adaptable to evolving analytical and regulatory demands.

Reference

1. U.S. Food and Drug Administration. PFAS in Medical Devices. FDA guidance and web information on PFAS considerations for medical devices, 2024–2026.
2. NAMSA. Impact of PFAS Regulations on Medical Devices. Industry perspective from a global medical device CRO.
3. AdvaMed. PFAS in MedTech; September 2025. Industry association report summarizing regulatory expectations and product impacts.
4. European Chemicals Agency. REACH Restriction Proposal on Per‑ and Polyfluoroalkyl Substances (PFAS) – Questions and Answers; 2026.
5. ECHA Committee for Risk Assessment (RAC) and Committee for Socio‑Economic Analysis (SEAC). Opinion on the PFAS restriction proposal under REACH; 2026.
6. Agilent Technologies. PFAS Consumables Ordering Guide; publication 5994‑2357EN, 2024. Guidance for PFAS‑suitable laboratory consumables.
7. ISO 10993‑12:2021. Biological evaluation of medical devices — Part 12: Sample preparation and reference materials; ISO, 2021.
8. U.S. Environmental Protection Agency. Method 1633: Analysis of PFAS in aqueous, solid, biosolids, and tissue samples by LC‑MS/MS; EPA 821‑R‑24‑001, 2024.
9. European Committee for Standardization. EN 17681‑1:2025. Textiles and textile products — PFAS analysis by LC‑MS/MS; CEN, 2025.