Testing of estradiol in a compounded cream and a stock solution

Potency testing (i.e., analysis of the concentration of the active ingredient) is an important part of the quality-control process for compounded preparations. However, concerns about the reliability and interpretation of potency testing results have been raised by compounding professionals. Standards detailed in United States Pharmacopeia Chapter 795 allow nonsterile preparations to be within 90% to 110% of the theoretical calculated and labeled quantity of active ingredient. Variability among independent testing laboratories could have significant implications for interpretaion of whether a compounded preparation meets these standards. The primary goal of this study was to characterize the variability among analytical testing laboratories when analyzing the potency of a nonsterile, compounded hormone cream (specifically, estradiol) and an estradiol stock solution used to compound the cream. Blinded to the theoretical concentration of the active ingredient, three analytical testing labs were sent samples and asked to determine the concentration and the percent potency in the samples. The stock solution samples were sent after the results for the cream were received. All three labs found the hormone cream to be within the acceptable Unied States Pharmacopeia range of 90% to 110%. Percent potency ranged from 95% to 103.1%, with an average of 98.5% +/- 4.2%. All labs also found the stock solution to be within acceptable United States Pharmacopeia range. The labs found an average of 6.21 +/- 0.24 mg/mL estradiol. The average difference between the lab and the theoretical concentration was 0.21 +/- 0.24 mg/mL. Percent potency ranged from 100% to 107.8%, with an average of 103.4% +/- 4.0%. This study found a variability of about 4% among labs when analyzing the same nonsterile compounded estradiol homrone cream. The magnitude of these variations was consistent when estradiol was combined with other ingredients in a compounded cream and when it was analyzed as a stock solution. Between-lab variability must be considered when interpreting whether a pharmacy's compounded preparation is within the United States Pharmacopeia potency critera.