Relationship between HPLC precision and number of significant figures when reporting impurities and when setting specifications.
The rounding of an analytical result is a process that should take into account the uncertainty of the result, which is in turn assessed during the validation exercise. Rounding rules are known in physical and analytical chemistry since a long time, but are often not used or misused in pharmaceutical analysis. The paper describes the theoretical background of the most common rules and their application to fix the rounding of results and specifications. The paper makes use of uncertainty values of impurity determination acquired during studies of reproducibility and intermediate precision with regards to 22 impurities of drug substances or drug products. As a general rule, authors propose the use of sound and well-established rounding rules to derive rounding from the results of the validation package.
Preclinical and Research Biostatistics, sanofi-aventis, 195 Route d'Espagne, 31036 Toulouse Cedex, France. christophe.agut@sanofi-aventis.com
Christophe
C
Agut
Audrey
A
Segalini
Michel
M
Bauer
Giovanni
G
Boccardi
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D008433:Mathematics; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D011786:Quality Control; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical
D004364:Pharmaceutical Preparations