Methodological Verification of Quality Standards

The purpose of method validation is to determine whether the established methodology is suitable for the analysis of the product. Especially for those generic drugs that are different from the reference drug (RLD) in terms of production process, preparation components, and analysis methods, pharmaceutical manufacturers are required to verify the quality standard to prove the accuracy and reliability of the analysis of related substances. Alfa Chemistry provides method validation services by performing systematic analytical method validation of quality standards.

Figure 1. Analytical method lifecycle. (Li, W. 2019)

Our Services

Preliminary Validation of Quality Standards

• Analytical method feasibility research
  • Quality comparison testing
  • Influencing factor testing
• Optimization of the prescription process

When the proposed method is not suitable, we optimize the prescription process or establish a new analytical method.

Analytical Method Validation of Quality Standards

Verification items:

Characters; identification (physical & chemical identification and spectral identification); general inspection items; microbiological testing (provide a complete method verification test); dissolution rate; related substances (provide a complete method verification test); content determination (provide a complete method verification test).

Validation characteristics

• Specificity
  • Identification
  • Purity analysis: ensure that the analytical method used can detect the accurate content of impurities in the analyte, such as related substances, heavy metals, solvent residues, etc.
  • Content determination: provide accurate results of the content or potency of the analyte in the sample

Specificity verification services: interference test, forced degradation test (acid and base hydrolysis, thermal degradation, photolysis, oxidation), Separation test, peak purity determination (diode array detection, mass spectrometry detection).

(1) Separation test

Diode Array Detector - peak purity determination

LC-MS - structure confirmation

(2) Forced degradation test

Forced degradation test is an important means to evaluate the quality consistency of generic drugs and RLDs. We identify whether the degradation pathway of the product is consistent with that of RLD, and is there any difference in degradants

Degradation items: acid and base hydrolysis, oxidation, thermal degradation (solid, aqueous solution)

• Limit of detection (LOD) and limit of quantitation (LOQ)

Method: signal-to-noise (SNR) ratio

LOQ: a signal-to-noise ratio of 10:1

LOD: a signal-to-noise ratio of 3:1

• Linear range
• Precision
  • Injection precision: verify the precision of instrument analysis
  • Repeatability/Intra-assay precision: verify the precision at shorter time intervals under the same operating conditions
  • Intermediate precision: verify the precision when a method is applied on different days, by different operators using different instruments
• Accuracy

Method: recovery test is employed to verify

Figure 2. Acceptance criteria of validation parameters. (Ravisankar, P.; et al. 2021)

Acceptance Criteria for Method Validation

• Titration analysis
• Ultraviolet-visible (UV-visible) spectrophotometry
• High performance liquid chromatography (HPLC) method

Why Cooperate with Alfa Chemistry

• Advanced testing equipment
• Conduct pharmaceutical equivalence studies in accordance with the latest technical standards
• Strictly follow the quality management system and SOPs to carry out project organization, coordination, monitoring and management services to ensure the quality of project operation
• Well-trained and experienced pharmaceutical analytical scientists and chemists
• Reliable and stable reference substances and experimental reagents