Analytical R&D and Quality Control

Analytical Services

Our analytical team provides all of the analytical R&D services needed for process development, GLP studies, and GMP manufacturing campaigns. Our analytical team works closely with our process chemists and engineers to ensure the success of each project.

Our services include, but are not limited to, method development, method verification / validation, reference standard certification, release testing, stability studies, and impurity separation and identification.

We are skilled at HPLC and GC method development and validation; structure elucidation using LC-MS, GC-MS, High Resolution-MS, NMR; stability studies; and solid state / form characterization and solubility and MSZW (meta-stable zone width) determination.

Our analytical department partners with scientists with strengths in areas including instrument skills and applications in LC-UV, LC-MS, LC-CAD, GC-FID, GC-MS, ICP-MS, IC, Prep-LC, high resolution MS and NMR for structure elucidation, and with strong organic chemistry backgrounds.

Our analytical chemists work very closely with synthetic chemists to understand the intended purpose for each analytical method development, and provide the phase appropriate method, when a method is developed for route scouting or process development.

Our analytical chemists also work very closely with the client to develop a method that helps resolve the client regulatory concerns.

Capabilities at a Glance

  • HPLC / GC method development for challenging separations including chiral separations
  • Method development and testing using LC/MS LC/CAD GC/FID GC/MS NMR TGA KF DSC FT-IR Polarimeter
  • Method transfer/validation
  • Reference standard certification
  • Separation and Characterization of impurities and degredants
  • cGMP release testing
  • cGMP raw material release testing
  • cGMP intermediate and API release testing
  • Stability studies: stability indicating method development and stability sample testing
  • Genotoxic impurity method development and testing
  • Forced Degradation Pathway Understanding

Services include:

HPLC and GC method development for challenging separations including chiral separations

Rationales for HPLC Method Development for the API Release

  1. Harmonize the testing of starting materials, intermediates and API in one method, if possible.
  2. Use the API method for in-process-control. Or use a shorter method, preferably with the same column and mobile phase combination / compositions to avoid error, in order to maximize the efficient use of each instrument.
  3. Apply a retrospective approach to method development. Start development first on the API method; then add the starting materials and intermediates to the method to check the overall method suitability.
  4. Evaluate method specificity during process development, in order to ensure that adequate specificity is provided for the current process.
  5. Conduct forced degradation to evaluate the method specificity for the degradants.

Forced Degradation and Understanding of Degradation Pathway

Design the experiment to generate appropriate amounts of degradants that are likely to occur during the stability study. The team consists of Ph. D. level organic chemists and analytical chemists to provide a comprehensive understanding of the degradation pathway.

Chiral Separations

  • A wide selection of chiral columns for use with the Column Spider provides for quick screening for chiral separations.
  • Experienced analytical chemists with training in organic chemistry provide for efficient and rational method development / optimization.
  • Extensive experience with compounds that contain 2 or more chiral centers.

Method Development with HPLC-CAD

Extensive experience with method development / optimization / troubleshooting using Charged Aerosol Detection (CAD).

Genotoxic Impurities

LC-MS and GC-MS for analysis of genotoxic impurities at ppm levels. Cost efficient strategy for monitoring them.

Method Verification / Validation

Each method verification / validation protocols are prepared following a phase-appropriate strategy and are subject to review by the client.

Methods can be developed in-house, adopted from the client, or transferred to a client’s designated laboratories.

Reference Standard Certification

Complete reference standard certification can be conducted in-house. The chemical characterization typically includes structure elucidation by NMR (proton and carbon peak assignment), HR-MS, FTIR, and UV. The physical characterization includes XRPD, DSC, DVS and PSD.

A characterization report is written upon request from the client, based on the filing requirements.

Characterization of impurities and degradants

Raw Material, Intermediate and API Release Testing

In-house specifications and test methods are developed to be fit for their intended purpose. The methods for API release are typically validated following a phase-appropriate strategy.

Stability Studies: GMP and non-GMP

  • ICH conditions:
    -20 ºC, 5 ± 3 ºC, 25 ± 2 ºC / 60 ± 5% RH;
    30 ± 2 ºC / 65 ± 5% RH;
    40 ± 2 ºC / 75 ± 5% RH
  • Photostability (typically conducted during forced degradation)
  • Phase-appropriate study and protocol
  • Stability study summary report is provided with the recommended storage conditions and the necessary statistical analysis.

Solid State / Particle Size / Form Characterization

Dedicated group with state-of-the-art instruments (See Crystallization R&D)

Analytical Equipment

Instruments Qualified / Calibrated for GMP Use
Agilent HPLC & UPLC systems / UV & MS
Thermo Dionex UPLC / CAD & UV
Agilent GC/FID with headspace and direct injection
Agilent GC/MS with direct injection
Nicolet Avatar FT-IR Spectrometer
OptiMelt Automated Melting Point
Metrohm KF Coulometer with direct sample introduction and sample oven
Mettler Toledo balance/Micro-balance
Stability Chambers/Freezers as being set up at the following conditions: -20 °C • 5°C • 25°C/60% RH • 30°C/65% RH • 40°C/75% RH
ICP-MS for elemental impurities
IC for counter ion determination
XRPD for crystal form determination
PSD for particle size determination
DSC/TGA for thermo analysis

Instruments for R&D
Agilent GC-MS systems
Agilent GC-FID systems
UPLC/High Resolution MS (Thermo Orbitrap Elite Velos/Waters Accurity)
Varian Inova NMR Systems 300 and 400 MHz
Bruker NMR Systems 400 & 500 MHz

QC Data Integrity: Part 11 Compliance