Mass balance is a fundamental concept in chemical and pharmaceutical analysis. It involves accounting for the total amount of a substance entering and leaving a system, ensuring that no material is lost or unaccounted for during the analysis process. Achieving accurate mass balance is crucial for the reliability and validity of your analytical results. Here’s a comprehensive guide on how to ensure mass balance when analyzing active ingredients.
Understanding Mass Balance
Mass balance, also known as material balance, is based on the principle of conservation of mass. In the context of chemical and pharmaceutical analysis, it means that the total weight percent of active ingredients, impurities, inorganics and residual solvents will add up to 100%.
Achieving mass balance
Weight % Assays:
The weight % of the AI and all identified impurities are determined using typically either liquid chromatography (LC), gas chromatography (GC) or Mass spectrometry (MS). Methods used should have been validated to ensure accuracy, precision and specificity. Also, internal standards and calibration curves should be used to correct for potential losses during analysis.
Residual solvents Analysis:
Residual solvents analysis are done using GC-FID to determine the residual solvents from the reactions that are in the active ingredient. This is done by making calibration curves with all solvents expected to be in the AI material and obtaining their weight percentages.
Inorganic Analysis:
Inorganics and metals are typically analyzed using IC and ICP-MS respectively. These techniques are employed to account for any inorganic impurity that still remains in the active ingredient.
Water content:
Karl Fischer titration is the preferred method for water content determination in pharmacopeias and countless norms, e.g. ASTM or DIN. Understanding the amount of water is vital to closing the mass balance.
Other tests:
Sometimes heavy components need to be determined using size exclusion chromatography when dimers and other polymeric impurities are formed in the reaction. For non-UV absorbing impurities, alternate detectors like the evaporative light scattering detector (ELSD) can be employed to identify and quantify these impurities so that the mass balance can be achieved.
Conclusion
Ensuring mass balance is a critical aspect of chemical and pharmaceutical analysis. By following these steps, you can achieve accurate and reliable results, contributing to the overall quality and integrity of your analytical work. Remember, meticulous preparation, precise measurements, and thorough documentation are also key to successful mass balance. Happy analyzing!