Relationship between content limits and assay methods: an interlaboratory statistical evaluation

Abstract

It has been statistically demonstrated, by means of interlaboratory acquired experimental results, that the prescribed content limits in a pharmacopoeial monograph should be critically reconsidered if one volumetric assay method is systematically substituted by another. Three different volumetric methods, prescribed as assays in phenothiazine monographs and ensuring the same content limit intervals, reveal different repeatabilities or reproducibilities. Analysis of variance and box-plot presentations confirm that for some of the three methods examined, interlaboratory variations contribute significantly to the total variances. For one particular method, however, this contribution is obviously less pronounced. Important contributions of method-to-method variations to the total variance are also established for three of the four participating laboratories.