Purity determination and uncertainty evaluation of theophylline by mass balance method, high performance liquid chromatography and differential scanning calorimetry.

Purity determination of pure organic substance is essential for the establishment of traceability to SI units. A mass balance method was employed to determine the purity of theophylline certified reference materials (CRM), compared with high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC). In the approach of the mass balance, the impurities were identified by ion trap time-of-flight mass spectrometer (IT-TOF-MS) and quantified by HPLC. The purity of theophylline CRM determined by mass balance method was 99.82% with an extended uncertainty of 0.1% (k=2). The uncertainty evaluation of purity demonstrated that the accuracy of the mass balance method is better than that of HPLC and DSC. It indicated that the mass balance is suitable for the CRM and pharmaceutical standards.