In the pharmaceutical industry, the Analytical Method Development for Active Pharmaceutical Ingredients (API) is crucial in ensuring the quality, safety, and efficacy of drugs. Within this, the Gas Chromatography (GC) Department plays a significant role, especially for APIs that require volatile and semi-volatile compound analysis. Here's an overview of how method development and validation are typically carried out in an API-GC Department:
1. Understanding the API Properties
- Physicochemical Properties: Assessing the API’s molecular weight, polarity, boiling point, and volatility helps in selecting appropriate GC conditions.
- Impurity Profile: Identifying potential impurities or degradation products helps design methods that ensure thorough separation and accurate quantification.
2. Method Development Process
- Selection of GC Columns: Choosing the appropriate stationary phase, column length, diameter, and film thickness based on the API's properties and impurities.
- Carrier Gas Optimization: Common carrier gases include helium, nitrogen, and hydrogen. Adjusting the gas flow rate and pressure affects sensitivity, peak shape, and retention times.
- Temperature Programming: Designing an optimal temperature program (isothermal or gradient) is essential to achieve good separation for both the API and impurities.
- Injector and Detector Optimization: Selecting and fine-tuning detectors (e.g., FID, TCD, ECD) that match the API’s properties and adjusting injection parameters for the sample matrix.
3. Method Validation
- Specificity: Ensuring the method distinguishes the API from impurities, excipients, and degradation products.
- Accuracy and Precision: Determining if the method reliably quantifies the API and impurities with minimal variability.
- Linearity and Range: Assessing the linearity of response over the desired concentration range.
- Sensitivity: Calculating the limit of detection (LOD) and limit of quantification (LOQ) to confirm the method's ability to detect low levels of impurities.
- Robustness: Testing the method’s resilience to small changes in conditions (e.g., temperature fluctuations, column variability).
4. Data Analysis and Reporting
- System Suitability Testing: Conducted before each analysis to confirm instrument performance.
- Data Analysis and Interpretation: Includes retention time, peak area, and height measurements, which help in the quantification and identification of impurities.
- Documentation and Reporting: Method development and validation findings are meticulously documented to comply with regulatory standards (e.g., ICH Q2 guidelines).
5. Compliance with Regulatory Requirements
- The GC methods developed for APIs must meet guidelines from agencies like the FDA, EMA, and ICH, focusing on accuracy, precision, and reproducibility.
- Ensuring Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP) during method development and validation processes.
Importance in the Pharmaceutical Industry
The API-GC Department is vital for the quality control of APIs, as it ensures the consistent purity and stability of compounds, directly affecting the safety and efficacy of pharmaceutical products. Analytical method development by GC also provides a reliable way to monitor impurities, residual solvents, and degradation products, helping maintain drug quality throughout production and shelf life.
Job Location: Andheri Mumbai
Qualification: M. Pharm or MSc Organic Chemistry/ Analytical Chemistry
Job Description:
Hands on Experience on GC-HS instrument, with exposure to method development, routine analysis/ partial validation analysis. Should be familiar with analysis of RM/KSM/API on GC for tests such as Residual solvent/Related substances/Chromatographic purity/Impurity content. Knowledge of GC Calibration and instrument troubleshooting is must. Should have worked in GLP environment.
Please share your cv at vishalb@macleodspharma.com
