Introduction
Extractables and leachables are important considerations in pharmaceutical analysis, chromatography, medical devices, packaging systems, and product-contact materials. These compounds can originate from container closures, vial septa, packaging components, tubing, manufacturing equipment, and delivery systems.
Because these materials come into contact with samples, drug products, or mobile phases, understanding the difference between extractables and leachables is essential for assessing product quality, regulatory compliance, and analytical reliability.
What Are Extractables?
Extractables are chemical compounds that can be removed from a material when it is exposed to aggressive or exaggerated laboratory conditions.
These studies typically use:
- Strong solvents
- Elevated temperatures
- Extended extraction times
- Simulated use conditions
- Accelerated testing protocols
The purpose of extractables testing is to identify compounds that have the potential to migrate from a material under worst-case conditions.
Examples of sources include:
- Vial septa
- Plastic packaging
- Bottle caps
- Tubing
- Manufacturing equipment
- Drug-delivery devices
Purpose of Extractables Studies
Extractables studies are designed to create a comprehensive chemical profile of compounds that may be present in a product-contact material.
These studies help:
- Identify potential contaminants
- Evaluate material suitability
- Support risk assessments
- Guide leachables investigations
- Assess supplier or material changes
Because extractables testing is performed under aggressive conditions, the detected compounds may not necessarily appear during actual product use.
What Are Leachables?
Leachables are compounds that migrate into a sample, drug product, or formulation under normal storage and use conditions.
Unlike extractables, leachables are generated during real-world exposure conditions such as:
- Product storage
- Product transport
- Shelf-life studies
- Routine use
Leachables represent compounds that are actually transferred into the product during its intended lifecycle.
Relationship Between Extractables and Leachables
Leachables are generally considered a subset of extractables.
A common way to describe the relationship is: All leachables are potential extractables, but not all extractables become leachables.
This is because extractables studies are intentionally designed to produce more extreme conditions than a product would ordinarily encounter.
As a result:
- Extractables identify what could migrate.
- Leachables identify what actually does migrate.
Why Leachables Are Important
Leachables may affect:
- Product quality
- Product stability
- Analytical accuracy
- Regulatory compliance
- Patient safety
For pharmaceutical products, leachables studies help determine whether packaging materials and container-closure systems remain suitable throughout the product's shelf life.
Material and Supplier Changes
Changes in manufacturing processes can alter the extractables and leachables profile of a product-contact material.
Examples include:
- Resin changes
- New additives
- Different mold-release agents
- Manufacturing process modifications
- Alternative raw material suppliers
These changes may introduce new compounds capable of migrating into the product. For this reason, when significant material changes occur, an Extractables and Leachables (E&L) evaluation is often recommended to determine whether new contaminants have been introduced.
Applications in Chromatography
Extractables and leachables are important considerations for:
- Autosampler vial septa
- Caps and closures
- Plastic containers
- Sample storage devices
- Tubing and fittings
- LC-MS applications
- Trace-level analyses
At very low analyte concentrations, even small amounts of contamination can affect chromatographic results and method performance.
Why LC-MS Methods Are Especially Sensitive
High-sensitivity LC-MS methods are particularly susceptible to contamination from extractable or leachable compounds.
Potential consequences include:
- Elevated background signals
- Unexpected chromatographic peaks
- Ion suppression
- Quantitation errors
- Reduced method sensitivity
For this reason, low-extractable packaging and sample-handling materials are commonly selected for LC-MS workflows.
Conclusion
Extractables and leachables both describe compounds that may migrate from product-contact materials into samples or products. Extractables are identified using exaggerated laboratory extraction conditions to evaluate worst-case migration potential, while leachables are compounds that migrate under normal storage and use conditions. Together, extractables and leachables studies provide critical information for material selection, product safety, regulatory compliance, and analytical method reliability.