Analytical Method Development

Proper development of analytical methods from the early stages of a drug development program is crucial. Even at early stages, to prevent costly delays and study repeats later, analytical method development must meet minimal criteria for resolution and quantitation, such that the analytical method may be optimized, qualified, and validated, as appropriate, in later stages of drug candidate development. This is particularly true for HPLC analytical methods, which are integral to many drug development activities.

Analytical support is required for a variety of purposes: at different stages of a drug development cycle, specifically in pre-formulation and formulation development, in salt-screening, in synthesis and manufacturing, for quality control and assurance, and for other applications.

Wolfe Laboratories Inc. develops and qualifies many types of analytical methods for its clients and the methods are tailored to project requirements. For example, qualitative assessment of solubility properties among a series of analogous compounds may be appropriate for a pre-nomination program. The data generated with such a method will be used to construct a relative rank-order of compounds in a series. Alternatively, rigorous quantitative measurement of properties of a compound nominated for clinical development may be needed. WLI excels at determination of thermodynamic solubility properties of compounds during pre-formulation and formulation development.

Typical analytical methods consist of two components: separation and detection. The majority of analytical methods used at Wolfe Laboratories are based on liquid chromatographic separation (HPLC) using common separation techniques. These include reverse and normal phase chromatography, size exclusion chromatography, and ion-exchange chromatography. Several types of detectors are available and their use is determined by properties of the analyte, most common are UV detectors for use in HPLC-UV analytical methods. Also used are evaporative light scattering detector (ELSD), refractive index (RI), and other detectors coupled to a HPLC system. The most sensitive and specific detector operated by WLI is a triple quadrupole mass spectrometer, which is used for LC-MS and LC-MS/MS analytical methods.

WLI performs analytical method development work with a variety of drug substances, including small molecules, peptides, proteins, oligonucleotides, and cytotoxic materials.