When Sustainability Meets Safety Requirements
Your laboratory is committed to adopting more sustainable practices. Reducing solvent consumption, minimizing hazardous waste, and choosing greener alternatives align with both environmental responsibility and corporate sustainability goals.
But for extractables and leachables analysis, there’s a non-negotiable constraint: you must recover all species. Missing even one potential leachable because your extraction solvent isn’t effective enough could mean overlooking a compound that poses genuine risk to product safety.
Can sustainable solvent alternatives deliver the comprehensive extraction performance that E&L analysis demands? Or does green chemistry require compromising on analytical thoroughness?
Watch: Systematic Evaluation of Green E&L Solvents
In this video, Resolian extractables and leachables scientist Sarah Norton presents systematic evaluation of sustainable solvent alternatives for GC-MS screening, comparing their performance directly against traditional extraction solvents.
The pharmaceutical industry’s increasing focus on sustainability has driven demand for greener laboratory practices across all analytical workflows. For extractables and leachables testing, this creates a unique challenge: the need to balance environmental responsibility with the absolute requirement for comprehensive compound recovery.
E&L analysis aims to identify all potential compounds that could migrate from packaging, delivery devices, or manufacturing equipment into pharmaceutical products. These extractables (compounds that can be extracted under exaggerated conditions) and leachables (compounds that actually migrate under normal use) must be comprehensively characterized to assess patient safety risks.
Any solvent substitution that reduces recovery of specific compound classes creates blind spots in safety assessment.
What You’ll Learn in This Video:
- The sustainability imperative driving solvent alternatives in pharmaceutical testing
- Why comprehensive recovery is non-negotiable for E&L safety assessment
- The three sustainable solvents selected for evaluation: 1,3-dioxolane, 2-MeTHF, ethyl(-)-L-lactate
- Variables investigated: liquid-liquid extraction ratios and salt addition
- Use of representative standard mixes spanning retention times and boiling points
- Phase separation results and initial screening outcomes
- Optimization findings: salt addition effects and ratio comparison (1:1 vs 10:1)
- BHT stabilizer consideration in sustainable solvents
- Direct performance comparison against traditional solvents (dichloromethane, hexane, ethyl acetate)
- Recovery data demonstrating equal or superior performance
Sarah’s systematic approach ensures that sustainability recommendations are backed by rigorous comparative performance data.
The Sustainable Solvent Candidates
Resolian selected three sustainable solvents for evaluation based on their potential as extraction media and their improved environmental profiles compared to traditional options:
1,3-Dioxolane: A cyclic ether with lower toxicity profile than traditional chlorinated solvents
2-Methyltetrahydrofuran (2-MeTHF): A bio-based solvent derived from renewable resources with favorable environmental characteristics
Ethyl(-)-L-lactate: A biodegradable ester with low toxicity and renewable sourcing potential
Each represents a different chemical class, providing diverse extraction mechanisms that could match the broad polarity range required for comprehensive E&L screening.
The Optimization Approach
Rather than simply testing sustainable solvents under standard conditions, Sarah’s team systematically optimized extraction variables to give each solvent the best opportunity to demonstrate performance:
Liquid-liquid extraction ratios: Testing both 1:1 and 10:1 ratios to determine optimal conditions for compound recovery
Salt addition: Investigating 2 molar sodium chloride addition to promote phase separation and enhance extraction efficiency
Representative standard mix: Spiking samples with compounds spanning different retention times and boiling points to assess recovery across diverse chemical classes
This optimization ensures fair comparison and identifies conditions where sustainable solvents perform at their best.
The Phase Separation Reality
Initial screening immediately eliminated one candidate. Ethyl(-)-L-lactate showed no phase separation, a fundamental requirement for liquid-liquid extraction workflows. Without clean phase separation, the solvent cannot effectively partition compounds from aqueous matrices.
Both 1,3-dioxolane and 2-MeTHF demonstrated good phase separation, advancing to further optimization studies.
Salt Addition: The Performance Enhancer
Testing with 2M sodium chloride revealed significant performance improvements. Salt addition increases ionic strength in the aqueous phase, promoting better phase separation and enhancing extraction efficiency for many compound classes.
Comparing 1:1 versus 10:1 liquid-liquid ratios showed that 1:1 delivered best overall recovery across the standard mix. This finding is significant because it means less solvent volume is required per extraction, further enhancing the sustainability profile.
The BHT Stabilizer Consideration
Analysis revealed that both 1,3-dioxolane and 2-MeTHF contain BHT (butylated hydroxytoluene) as a stabilizer to prevent peroxide formation. This presents an important analytical consideration: BHT is a compound frequently detected as a leachable in pharmaceutical products.
Laboratories using these solvents need awareness that BHT presence from the extraction solvent could potentially interfere with detection of BHT as a leachable from the product itself. This requires consideration during method development and result interpretation but doesn’t disqualify the solvents for E&L use.
Performance Versus Traditional Solvents: The Critical Comparison
The ultimate test: how do these sustainable alternatives compare against the traditional solvents they aim to replace?
Sarah’s team compared recovery of the standard mix using:
- Traditional: Dichloromethane, hexane, ethyl acetate
- Sustainable: 1,3-dioxolane, 2-MeTHF (under optimized conditions)
The results demonstrated that both sustainable solvents showed recoveries equal to or exceeding traditional solvents across the tested compound classes.
This comparative data provides the confidence needed to adopt sustainable alternatives: they don’t require compromising on extraction performance or safety assessment comprehensiveness.
Green Chemistry Without Compromise
Sarah’s evaluation demonstrates a crucial principle: sustainability and analytical performance aren’t inherently competing priorities. With systematic evaluation and optimization, green chemistry alternatives can match or exceed traditional approaches while reducing environmental impact.
For extractables and leachables testing, this means:
- Lower environmental footprint through reduced hazardous solvent use
- Maintained or improved compound recovery across diverse classes
- Confidence in comprehensive safety assessment
- Alignment with corporate sustainability commitments
- Potential cost benefits from improved extraction ratios
Expert E&L Analysis with Environmental Consciousness
Resolian’s extractables and leachables team combines deep technical expertise in safety assessment with commitment to sustainable analytical practices. Our approach includes:
- Systematic evaluation of green chemistry alternatives
- Optimization studies ensuring sustainable options perform at their best
- Comprehensive method validation for regulatory confidence
- Experience with diverse product matrices and delivery systems
- Global laboratory capabilities supporting multi-region projects
Whether you’re seeking routine E&L testing or exploring sustainable solvent transitions for your analytical workflows, we bring both the technical rigor and environmental consciousness that modern pharmaceutical development requires.
Ready to discuss sustainable approaches to extractables and leachables testing?
Contact our E&L team to explore how green chemistry alternatives can meet your analytical and sustainability goals.
