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Pharmaceutical & Biopharmaceutical Development Services

EAG brings unparalleled expertise to the development and commercialization of small molecule drugs, biopharmaceuticals, antibody-drug conjugates (ADCs), drug-device combination…

EAG brings unparalleled expertise to the development and commercialization of small molecule drugs, biopharmaceuticals, antibody-drug conjugates (ADCs), drug-device combination products and other therapies. From designing IND-enabling studies to delivering full CMC analytical and QC support, we join your R&D team as a true partner. EAG scientists take time to understand both your commercial goals and the unique characteristics of your compound. We provide expert guidance to balance regulatory expectations with expediency and cost, and approach technical challenges with flexibility and resolve.

Materials Testing & Analysis

When it comes to understanding the physical structure, chemical properties and composition of materials, no scientific services company offers the breadth of experience, diversity…

When it comes to understanding the physical structure, chemical properties and composition of materials, no scientific services company offers the breadth of experience, diversity of analytical techniques or technical ingenuity of EAG. From polymers to composites, thin films to superalloys—we know how to leverage materials sciences to gain a competitive edge. At EAG, we don’t just perform testing, we drive commercial success—through thoughtfully designed investigations, technically superior analyses and expert interpretation of data.

Environmental Testing & Regulatory Compliance

Having helped develop the test methods that shape current regulatory guidelines, EAG chemists, biologists and toxicologists have evaluated the environmental impact of thousands of…

Having helped develop the test methods that shape current regulatory guidelines, EAG chemists, biologists and toxicologists have evaluated the environmental impact of thousands of active ingredients and formulations—from pesticides and pharmaceuticals to industrial chemicals and consumer products. Whether you are exploring “what if” scenarios, registering a new active ingredient or formulation, responding to a data call-in or seeking to understand the latest guidance, turn to EAG for technical excellence, sound advice, GLP-compliant study execution and expert interpretation.

Microelectronics Test & Engineering

Whether connecting the internet of things, guiding surgical lasers or powering the latest smart phone, integrated circuits and microelectronics touch nearly every aspect of human…

Whether connecting the internet of things, guiding surgical lasers or powering the latest smart phone, integrated circuits and microelectronics touch nearly every aspect of human life. In the world of technology, innovation and continuous improvement are imperatives—and being able to quickly and reliably test, debug, diagnose failures and take corrective action can make the difference between a doomed product launch and building a successful global brand. EAG offers you the world’s largest and most diverse collection of specialized analytical instrumentation, capacity to perform a variety of microelectronic tests in parallel, and the multi-disciplinary expertise required to draw true insight from data.

Custom Synthesis & Radiolabeling

No contract service provider has more experience performing custom synthesis and producing isotopically labeled compounds to support product development in life science, chemical…

No contract service provider has more experience performing custom synthesis and producing isotopically labeled compounds to support product development in life science, chemical and related industries than we do. From 14C and 3H radiolabeled clinical trial materials synthesized under cGMP, to stable-labeled active ingredients for metabolism and environmental fate/effects testing, turn to EAG. We have extensive experience with multi-step and other complex synthesis projects, and our comprehensive, in-house analytical services ensure quick turnaround of purity and structural confirmation.

Crop Biotechnology & Development

EAG combines biotechnology and protein characterization expertise with more than 50 years' experience analyzing chemical compounds in plant and environmental matrices to address…

EAG combines biotechnology and protein characterization expertise with more than 50 years’ experience analyzing chemical compounds in plant and environmental matrices to address the growing needs of the biotechnology crop industry. We offer a wide range of techniques required to fully characterize the event insertion and expressed proteins, as well as the various studies required to confirm the food, feed and environmental safety of products that represent the trait. From early-stage protein confirmation to GLP-compliant EDSP and allergenicity testing, we help you make faster, more informed development decisions and comply with evolving global regulations of genetically engineered crops.

Litigation Support & Expert Testimony

When you need solid science and investigative engineering to address product failures, inform legal strategy, protect intellectual property or address product liability disputes,…

When you need solid science and investigative engineering to address product failures, inform legal strategy, protect intellectual property or address product liability disputes, turn to EAG. We’ve provided technical consulting, analysis and expert testimony for hundreds of cases involving the aerospace, transportation, medical device, electronics, industrial and consumer product industries. Our team of experts understands the legal process and your need for responsiveness, effective communication, scientifically defensible opinion and confidentiality. From professional consulting to data review to trial preparation and expert witness testimony, ask EAG.

Techniques

Chromatography

Using an array of advanced separation techniques and innovative technology, we conduct highly precise analytical chromatography for various industries. Whether you want a closer…

Using an array of advanced separation techniques and innovative technology, we conduct highly precise analytical chromatography for various industries. Whether you want a closer look at the purity of your pharmaceutical or need to better understand an agrochemical’s components, EAG has the expertise to separate and evaluate any compound.

Mass Spectrometry

Need to evaluate the molecular structure of a compound or identify its origins? EAG knows how. With state-of-the-art tools, we can separate, vaporize and ionize the atoms and…

Need to evaluate the molecular structure of a compound or identify its origins? EAG knows how. With state-of-the-art tools, we can separate, vaporize and ionize the atoms and molecules in almost any pure or complex material to detect and obtain mass spectra of the components. We rely on decades of experience in mass spectrometry to provide our clients with precise analyses and the best detection limits.

Imaging

EAG is a world leader in high-resolution imaging down to the atomic level. We offer unmatched analytical know-how, generating extremely detailed surface and near surface images…

EAG is a world leader in high-resolution imaging down to the atomic level. We offer unmatched analytical know-how, generating extremely detailed surface and near surface images for various industries, from consumer electronics to nanotechnology. Using state-of-the-art equipment and innovative techniques, we conduct expert imaging to aid in failure analysis, dimensional analysis, process characterization, particle identification and more. If you want to investigate a material with angstrom scale resolution, you can count on EAG to get the job done quickly and precisely.

Spectroscopy

EAG offers a vast array of spectroscopic techniques to clients in various industries, from defense contractors to technology pioneers. We combine unparalleled expertise and…

EAG offers a vast array of spectroscopic techniques to clients in various industries, from defense contractors to technology pioneers. We combine unparalleled expertise and methodology with cutting-edge technology to analyze your organic, inorganic, metallic and composite materials for identification, compositional, structural and contaminant information. Whether you need expert spectroscopic analysis to improve your production process or to surmount a technical challenge, EAG is up to the task.

Physical/Chemical Characterization

Need to identify your unique material? Want to analyze the thermal properties of a sample, or measure the success of a process step? If it has to be done quickly and it has to be…

Need to identify your unique material? Want to analyze the thermal properties of a sample, or measure the success of a process step? If it has to be done quickly and it has to be done right, you can count on EAG. We offer a range of adaptable techniques and innovative methods to evaluate the physical and chemical characteristics of any compound. Our highly precise testing and analytical services will improve your production process, expedite R&D and help you conquer any technical challenge.

About

A Global Scientific Services Company

One of the most respected names in contract research and testing, EAG Laboratories is a global scientific services company operating at the intersection of science, technology and…

One of the most respected names in contract research and testing, EAG Laboratories is a global scientific services company operating at the intersection of science, technology and business. The scientists and engineers of EAG apply multi-disciplinary expertise, advanced analytical techniques and “we know how” resolve to answer complex questions that drive commerce around the world.

Our Customers

Science and technology transcend industry boundaries, and so does demand for EAG’s expertise. We partner with companies across a broad spectrum of high-tech, high-impact and…

Science and technology transcend industry boundaries, and so does demand for EAG’s expertise. We partner with companies across a broad spectrum of high-tech, high-impact and highly regulated industries. We help our customers innovate new and improved products, investigate manufacturing problems, perform advanced analyses to determine safety, efficacy and regulatory compliance, and protect their brands.

Our Company Culture

EAG’s corporate culture is firmly rooted in four guiding principles: “foster a growth mindset,” “find a better way,” “earn more loyal customers,” and “win…

EAG’s corporate culture is firmly rooted in four guiding principles: “foster a growth mindset,” “find a better way,” “earn more loyal customers,” and “win together.” Across all of our 20+ locations, you will find a true passion for science and the power of science to improve the world we live in. Hear what some of our ~1200 scientists, engineers and support personnel say about what it means to be part of EAG Laboratories.

Careers

EAG is growing, and we are always looking for talented, problem-solving oriented individuals to join our company. If you have a “we know how” spirit, we want to hear from you.…

EAG is growing, and we are always looking for talented, problem-solving oriented individuals to join our company. If you have a “we know how” spirit, we want to hear from you. Browse current openings now, and re-visit our careers page often.

How do you drive R&D productivity and keep up with regulations?

Challenges for Analysis of Pyrethroid Residues: Overall Strategies and Solid Phase Micro-Extraction (SPME) Case Study

APPLICATION NOTE

By Del A. Koch, John Owen and Kevin L. Clark

INTRODUCTION

Pyrethroid insecticides play an important role controlling insect pests in agriculture and home and lawn care, and also in protecting humans and animals from parasites. They thus can sometimes be found at low levels in environmental samples; therefore accurate and highly sensitive analysis of pyrethroids in various matrices is important. Analysis of pyrethroids has some challenging aspects; strategies for meeting these challenges, with an emphasis on SPME analysis, will be presented.

ANALYTICAL CHALLENGES AND RESPONSES

Challenge: Pyrethroids have extremely low water solubility values and tend to sorb onto particulates and container walls, requiring special care for handling/preservation of aqueous samples.

Response: Immediately after collection, methanol and hexane are added to the aqueous sample to reduce (and possibly reverse) adsorption to container walls. When ready for analysis the entire container is shaken and the hexane layer is removed, followed by a final hexane rinse of the entire container after sample transfer.


Challenge: The instrument of choice for multi-analyte pyrethroid methods is negative chemical ionization gas chromatography with mass spec detection (NCI-GC-MS), which is prone to variability due to differential matrix effects (i.e., sample extracts vs. solvent standards) in the inlet, as well as detector drift.

Response: The addition of 0.1% peanut oil as an “analyte protectant” has helped to smooth out inlet eects and maintain sharper peak shapes. More signicantly, deuterium (d6) stable isotope analogues were custom synthesized and are being used as internal standards to normalize instrumental response.


Challenge: The multi-analyte method has been applied to complex matrices such as wastewaters and biosolids from Publicly Owned Treatment Works (POTWs). The evaluation of method performance is complicated by the lack of analyte-free materials for fortification purposes and the sample-to-sample variability that implies that recoveries measured from a given biosolids sample may not represent the method performance for a biosolids sample from another POTW source.

Response: It has been empirically determined that two of the eight pyrethroids (d6-esfenvalerate and d6-fenpropathrin) are suitable as surrogates that are added to all samples for evaluation of method performance. Because these d6 materials could not be used as instrumental internal standards to accurately and precisely quantify native esfenvalerate and fenpropathrin, respectively, experimentation indicated that deltamethrin-d6 and bifenthrin-d6, respectively, served adequately as “replacement” internal standards for the quantification of native esfenvalerate and fenpropathrin, respectively.


Challenge: The conventional approach to analyzing water samples measures total pyrethroid content, including any residues binding to non-filterable (or non-filtered) particulates or complexing with dissolved organic carbon – this approach does not determine the bioavailable concentrations.

Response: Use of an alternate technique – Solid Phase Micro-Extraction (SPME) – has been applied to the immediate (without storage) analysis of aqueous fractions, allowing accurate measurement of the bioavailable pyrethroid component of the sample, as discussed in more detail on the following page.

ANALYTICAL CHALLENGES AND RESPONSES

ANALYTICAL CHALLENGES AND RESPONSES

ANALYTICAL CHALLENGES AND RESPONSES

When applied to the immediate (without storage) analysis of aqueous fractions, Solid Phase Micro-Extraction (SPME) allows for the accurate measurement of the bioavailable pyrethroid component of the sample. This measurement of the bioavailable pyrethroid componentis not possible using conventional approach to analyzing water samples.

When applied to the immediate (without storage) analysis of aqueous fractions, Solid Phase Micro-Extraction (SPME) allows for the accurate measurement of the bioavailable pyrethroid component of the sample. This measurement of the bioavailable pyrethroid component is not possible using conventional approach to analyzing water samples.

SPME CASE STUDY

Pyrethroids in aqueous solution equilibrate among a freely dissolved phase (see below) and various noncovalently-bound phases. These equilibria strongly favor bound states over the freely-dissolved state. Only the freely-dissolved phase is bioavailable to organisms in the water column, and dissolved and suspended organic compounds can reduce pyrethroid bioavailability by competing with organisms for the freely dissolved phase.

This model is supported by experiments showing that pyrethroid uptake and toxicity in Daphnia and Cereodaphnia species are correlated with the activity (freely dissolved concentration), rather than the total concentration, of pyrethroid. Similar to aquatic organisms, a PDMS-coated SPME fiber introduced into the water absorbs an amount of pyrethroid that is directly proportional to the pyrethroid activity. SPME thus provides an attractive tool for measuring an endpoint that is both ecotoxicologically relevant and otherwise difficult to measure.¹

Stable isotope-labeled internal standards enable simultaneous determination of activity and total concentration. In our experiments with sediment pore water, deuterated analogs of the pyrethroids under study were added to pore water samples in known amounts. Samples were then vortexed and sonicated to ensure equilibration of the added internal standard.

SPME provides an attractive tool for measuring an endpoint that is both ecotoxicologically relevant and otherwise difficult to measure.

SPME provides an attractive tool for measuring an endpoint that is both ecotoxicologically relevant and otherwise difficult to measure.

Since the deuterated compound binds to every system component to the same extent as the analyte, quantitation based on the internal standard-corrected instrument response yields the total analyte concentration, while quantitation based on uncorrected instrument response (external standard calculation) yields the activity, both from the same GC-MS injection.²

At EAG Laboratories, SPME measurements were applied to the analyses of “pore water” samples (generated via the centrifugation of wet sediment), with the goal of determining the ratio of the pyrethroid concentrations in the sediment to the freely dissolved (and thus bioavailable) concentrations in the pore water.

Figure 2. SPME measurements are applied to the analyses of “pore water” samples, with the goal of determining the ratio of the pyrethroid concentrations in the sediment to the freely dissolved concentrations in the pore water.

Figure 2. SPME measurements are applied to the analyses of “pore water” samples, with the goal of determining the ratio of the pyrethroid concentrations in the sediment to the freely dissolved concentrations in the pore water.

Figure 3. Preparation of Pond Sediment Pore Water.

Figure 3. Preparation of Pond Sediment Pore Water.

Photo above shows three pore water samples in SPME analysis vials. In order to minimize the adsorption onto the walls of these SPME sample vials, analysis of the generated pore water samples was performed as quickly as feasible following the generation of samples via centrifugation. Also, the calibration standards (in water) were prepared one at a time, each immediately before use.

In order to facilitate the SPME measurements within a reasonable analysis time, a non-equilibrium (and thus non-depletive) approach was used. This technique requires strict control of the analysis parameters. The same fiber was used for a given batch of analyses, and a Gerstel autosampler/autoinjection system was used to maintain a constant sampling time and a consistent injection technique. In addition the autosampler swirled the contents of the standard and sample vials during the SPME sampling process.

The pyrethroid activity is known only when the activity is the same as the total concentration. This condition is met in pure water (in the absence of dissolved organic compounds). Pure water was therefore used to prepare calibration curves.

Table 1. Bifenthrin External Standard (top) and Internal Standrd (bottom).

Table 1. Bifenthrin External Standard (top) and Internal Standrd (bottom).

Table 1. Bifenthrin External Standard (top) and Internal Standrd (bottom).

Curves were plotted based upon raw peak areas and analyteinternal standard response ratios. The freely-dissolved analyte values were calculated from the raw peak area curves, and the total analyte values were calculated from the analyte-internal standard response ratio curves, using the approach described by Bondarenko and Gan. An example curve of each type, generated from the same experiment, is shown below.²

POSSIBLE FURTHER APPLICATIONS OF SPME

The selectivity of SPME in measuring the bioavailable portion of pyrethroids in aqueous systems has potential applications for passive sampling of streams and other natural water systems. Analysis of the adsorbed pyrethroids could be accomplished either by transfer of the adsorbed pyrethroids into the GC inlet via specialized equipment, or extraction of the sorbed component via organic solvent, followed by NCI-GC-MSD analysis.

ACKNOWLEDGEMENTS

The assistance and responsiveness of Kalexsyn, Inc. in supplying the stable isotope internal standards and surrogates are gratefully acknowledged. The collaboration and support of the PWG member companies (AMVAC, BASF, Bayer, FMC/Cheminova, Syngenta, and Valent) were key factors in the successful development of the analytical methods, and are greatly appreciated.

REFERENCES

¹Yang, W., et al., J Agric Food Chem 2006, 54, 3967-3972.

²Bondarenko, S., and Gan, J. Environ Sci Technol 2009, 43, 3772-3777.