Top 5 Analytical Techniques Used in Extractables and Leachables Analysis (LC-MS, GC-MS, ICP-MS)

In pharmaceutical and medical device development, Extractables and Leachables Analysis plays a critical role in ensuring patient safety and regulatory compliance. Extractables and Leachables (E&L) studies detect potentially harmful chemicals that may migrate from packaging, delivery systems, or manufacturing components into the final drug product. To deliver accurate and reproducible data, cutting-edge analytical techniques are essential.

At ResolveMass Laboratories Inc., we specialize in advanced Extractables and Leachables Analysis services using high-resolution instrumentation and method validation approaches tailored to the stringent demands of global regulatory agencies. In this blog, we explore the top 5 analytical techniques used in Extractables and Leachables Analysis, and how each is vital to robust, reliable data generation.

1. Liquid Chromatography-Mass Spectrometry (LC-MS) for Extractables and Leachables Analysis

LC-MS is the gold standard for detecting semi-volatile and non-volatile organic compounds in Extractables and Leachables Analysis. It combines the separation power of liquid chromatography with the detection sensitivity of mass spectrometry. At ResolveMass Laboratories, our scientists employ LC-MS/MS systems capable of ultra-trace quantitation, often down to parts-per-trillion levels.

• Use Case: Identification of drug-contacting material impurities, degradation products, and plasticizers.
• Advantages: High sensitivity, selectivity, and ability to analyze thermally labile or polar compounds.
• Example Application: Detection of phthalates and antioxidant degradation products.

Explore our advanced LC-MS workflows for E&L testing

2. Gas Chromatography-Mass Spectrometry (GC-MS) for Extractables and Leachables Analysis

GC-MS is another cornerstone of Extractables and Leachables Analysis, particularly effective for volatile and semi-volatile organic compounds. Using thermal desorption or solvent extraction techniques, GC-MS helps uncover a wide range of leachables including residual solvents and monomers.

• Use Case: Analysis of extractable organic volatiles from plastic bags, tubing, stoppers, and container-closure systems.
• Advantages: Robust compound libraries for identification, high resolution, and reproducibility.
• Example Application: Detection of acetophenone and toluene derivatives in elastomeric closures.

Learn more about GC-MS analysis in our E&L studies

3. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for Extractables and Leachables Analysis

ICP-MS is the technique of choice for detecting elemental extractables in Extractables and Leachables Analysis. These may include heavy metals such as arsenic, lead, and cadmium that can leach from glass, rubber, or stainless steel.

• Use Case: Quantification of elemental impurities in packaging and processing equipment.
• Advantages: Extremely low detection limits and multi-element analysis capabilities.
• Example Application: Trace metal analysis in prefilled syringes and infusion systems.

Find out how we apply ICP-MS to metal leachables

4. Fourier-Transform Infrared Spectroscopy (FTIR)

FTIR is a powerful tool in characterizing unknown extractable compounds based on molecular vibrations. Though less sensitive than MS-based methods, it is invaluable for confirming compound classes and polymer residues.

• Use Case: Structural elucidation of non-volatile extractables and residue identification.
• Advantages: Rapid identification of compound classes, supports structural confirmation.
• Example Application: Identifying polymeric backbone residues in medical devices.

Read more on FTIR characterization in our testing services

5. Ultraviolet-Visible Spectroscopy (UV-Vis)

While not as selective as mass spectrometry techniques, UV-Vis provides a fast screening method for chromophoric extractables such as antioxidants and stabilizers in polymeric systems.

• Use Case: Routine monitoring of extractables in stability studies.
• Advantages: Quick and cost-effective for known chromophores.
• Example Application: UV screening of stabilizers in blow-fill-seal containers.

See how UV-Vis fits into our E&L analytical toolbox

Why Choose ResolveMass for Extractables and Leachables Analysis?

ResolveMass Laboratories Inc. brings decades of pharmaceutical analytical testing experience. We understand the regulatory frameworks including USP <1663>, <1664>, ICH Q3D, and various ISO standards relevant to packaging systems and drug-device combination products. Our multidisciplinary team leverages validated methods and Good Laboratory Practice (GLP) compliance for all Extractables and Leachables Analysis projects.

We have supported clients across:

• Biologics and biosimilar development
• Inhalation and nasal drug delivery
• Ophthalmic and injectable formulations
• Medical device sterilization compatibility

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Conclusion

When it comes to safeguarding drug product safety and achieving regulatory approval, choosing the right analytical partner for Extractables and Leachables Analysis is paramount. The use of advanced techniques such as LC-MS, GC-MS, ICP-MS, FTIR, and UV-Vis ensures that every risk is thoroughly evaluated. At ResolveMass Laboratories, our commitment to scientific excellence, regulatory alignment, and technical innovation positions us as a preferred E&L testing provider.

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ResolveMass Laboratories Inc. is a trusted Canadian contract research organization offering a wide spectrum of specialized services spanning polymer synthesis, advanced analytical testing, and custom organic synthesis. With over a decade of experience supporting pharmaceutical, biotech, and industrial clients, we bring scientific precision and regulatory insight to every project. Our core capabilities include Polymer Synthesis and Characterization, Peptide Characterization, Organic Synthesis, Nitrosamine Testing and Analysis, PFAS Testing, and Extractable & Leachable Studies, as well as a broad suite of analytical techniques such as HPLC, GC-MS, MALDI-TOF, NMR, and FTIR.  

Our multidisciplinary team includes chemists, analytical scientists, and regulatory experts with advanced academic and industry backgrounds. We excel at developing customized, high-quality solutions—whether you need innovative polymer designs, impurity profiling, or confirmatory testing that meets global regulatory standards.  

Clients across North America choose ResolveMass Laboratories for our deep technical knowledge, commitment to quality, and ability to deliver reproducible, reliable data that drives confident decision-making. When precision, innovation, and trust matter—ResolveMass is your partner of choice. 

References: 

1. • ICH Q8(R2) Pharmaceutical Development (Aug 2009).  

2. • ICH Q9 Quality Risk Management (Nov 2005).  

3. • FDA Guidance to Industry, Container Closure Systems for Packaging Human Drugs and Biologics (May 1999).  

4. • FDA Guidance to Industry (draft), Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products (November 1998).  

5. • FDA Guidance for Industry, Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products (July 2002).  

6. • PQRI Recommendation (draft), Safety Thresholds and Best Practices for E/L in Orally Inhaled and Nasal Drug Products (September 2006).