ABSTRACT
Control materials with reference values (RMVs) are gaining increasing importance in clinical chemistry and have become mandatory in Germany. According to the legal regulations in the FRG, theophylline (THP) is the first drug for which quality assessment based on reference method values is required. So far, however, a reference method for theophylline has not been established. Different analytical principles are desirable for the determination of highly accurate reference method values, especially if a definitive method is lacking. In this chapter, the authors report on two different methods for the determination of THP reference method values: high-performance liquid chromatography (HPLC) and isotope-dilution mass spectrometry (ID-MS). In the HPLC procedure, calibration is performed by use of standard addition. RMVs were assigned to control materials, and method-dependent values were compared with RMVs. Reference method values for theophylline determined by the described HPLC procedure are in good agreement with those obtained by ID-MS.
