Many of the projects EKG Labs takes on require at least some element of method transfer, whether with or without additional development. Method transfer projects requiring regulatory elements generally fall into one of three categories.
Method Verification: An externally validated method or a compendial method is directly transferred under EKG standard operating procedures.
Method Validation: An externally or internally developed method is rigorously evaluated by parameters such as Limit of Detection, Limit of Quantitation, Accuracy, Precision, Linearity, and Specificity to show its suitability for sample analysis.
Method Development: A method is developed internally and, assuming regulatory needs, is validated before implementation for sample analysis. EKG develops methods by relying on our years of expertise and familiarity with pharmaceutical products and by researching scientific literature for insight. In some cases, client-provided methods are optimized for better sensitivity, resolution, etc. Some methods need to be adapted for EKG instrumentation.
For example, during one EKG project, a client wanted an HPLC method utilizing a phosphate buffer to be adapted for MS compatibility. EKG mapped and transferred the phosphate buffer to an acetate buffer without compromising detectability and while maintaining retention time and gradient parameters.
EKG also develops methods for a large number of R&D projects, where formal validations and/or verifications are not necessary.
A Unique Case Study
EKG Labs was contacted with an unusual request: to convert a client-provided gas chromatography (GC) method to a liquid chromatography (LC) method and identify several impurity peaks. The client had been unable to obtain conclusive identifications of potential degradants using the limited fragmentation observed by GC. While EKG regularly performs impurity identifications, this was a unique challenge.
EKG started by first directly transferring the GC method to our GCMS to ensure our peak pattern matched our client’s and to evaluate the fragmentation data we were able to obtain.
Then, EKG developed an LC gradient method with water and acetonitrile (both containing 0.1% formic acid) that mimicked the GC method. We utilized the peak patterns and MS spectra profile matching to confirm the identities of the peaks of interest. Analytical scale fractionation assisted in method transfer by collecting fractions off the HPLC, and analyzing these fractions individually by both GCMS and LCMS. All peaks were identified, most traceable to starting materials.
Learn more about method development at EKG Labs by reading additional case studies:
- HPLC Detection of PAHs in Challenging Matrices
- Analyzing Deuterium Content in Pharmaceuticals
- Separation of Co-eluting Impurities
About EKG Labs
EKG Labs is an analytical service provider for the medical device and pharmaceutical industries. Our analytical services support regulatory filings, product development, and analytical chemistry investigations. EKG regularly develops and validates methods for pharmaceutical assay, impurity investigations, and more.
Additional specialty analytical services include: extractables, leachables, a variety of USP testing, biocompatibility (ISO 10993), characterization, deformulation, and other investigational activities.
If you are experiencing a challenge with development and validation of a difficult method or need analytical services to support your product development, please contact us us at 810-354-5229.