Analytical characterization involves a variety of techniques and addresses different phase-appropriate needs. Analytical characterization of a drug substance, in solution and in solid state (solid state characterization or SSC) is an important part of early lead selection and optimization programs, and encompasses physicochemical characterization for solubility and stability, and measurement of other properties that affect a compounds development potential. A progressively higher level of rigor is applied in developing the analytical methods as the lead optimization program moves into development. Analytical characterization methods and data are the foundation of the chemistry, manufacturing, and controls (CMC) section of the IND filings.
Analytical support is required for a variety of purposes: at different stages of a drug development cycle, 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 provides analytical characterization work with a variety of drug substances, including small molecules, peptides, proteins, oligonucleotides, and cytotoxic materials.