Korean MFDA update guideline–
The document serves as a comprehensive reference for validated analytical methods used to detect and quantify impurities in pharmaceutical products, with a focus on ensuring drug safety and regulatory compliance. It emphasizes the importance of method validation or verification before application, acknowledging that while the methods are standardized, they must be adapted to specific laboratory conditions. The guide includes detailed protocols for detecting various impurities such as nitrosamines, azido compounds, and alkyl sulfonates, which are known for their potential genotoxic or carcinogenic effects.
Additionally, the document outlines the scientific rationale behind each method, including sample preparation, instrumentation, and data evaluation. The analytical techniques described involve the use of LC-MS/MS and GC-MS/MS, among others. It also provides guidance on developing new impurity testing methods, considering the chemical nature of impurities and the characteristics of the drug matrix.
The contents are as follows:
1. Nitrosamine Impurities Analysis Methods
- Methods for NDMA/NDEA Analysis
- Methods for NDSRI Analysis
- Analysis Methods for Occurrence Cause
2. Other Impurities Analysis Methods
- Azido Impurities Analysis Methods
- Alkyl Sulfonate Impurities Analysis Methods
- Other Analysis Methods
Appendix: Procedure for Developing New Impurity Test Methods
This revision brought the following changes:
- A new analysis method for 20 types of NDSRIs in Finished Pharmaceuticals [LC-MS/MS] has been added (Item 25)
- The analysis method for nitrites in pharmaceutical excipients has been expanded from covering 8 types (split across two methods in 2025) to a single comprehensive method covering 11 types of excipients.
- Tightens quantitation/detection limits and clarifies validation parameters for several items.
This document supersedes 2025 Compilation of Analysis Methods on the Determination of Impurities in Pharmaceuticals, May-2025
Original document here:
IDRAC_429242_18-May-2026_MFDS Guideline_ Compilation of Analysis Methods on the Determination of Imp.pdf (1.6 MB)
Tranlation (provided by Google machine translation):
Machine Translated Document - IDRAC 429242.pdf (33.3 MB)