Application of new data processing method for the photodiode array detector in the drug substance analysis.

While analyzing active pharmaceutical ingredients (APIs) it is necessary to determine both the assay of the drug substance itself and the content of impurities in a drug substance. The ideal situation is when both assay of drug substance and content of related substances can be determined simultaneously (1). However, as the impurities must be determined at relatively low levels, it is often impossible to select such analytical conditions, which allow to determine both the API assay and the content of impurities in one chromatographic run. Drug substance concentration in a method for the determination of its purity is often outside the linear range of the applied detector and an additional analytical procedure for the drug substance assay must be developed (2, 3). An Intelligent Dynamic Range Extension Calculator (i-DReC) is a new data processing method for the photodiode array detector, available in the LabSolutions software by Shimadzu. It allows to extend the linear range of chromatographic method by shifting the chromatographic profile to the wavelength where the target signal is not saturated. The peak area of the acquired chromatogram is corrected by the factor of the absorption ratio between the original target wavelength and the wavelength used by the i-DReC function. The iDReC is applied automatically when the intensity of the target peak exceeds the user-defined threshold value (4, 5). Temozolomide (3,4-dihydro-3-methyl-4oxoimidazo-[5,1-d]-as-tetrazine-8-carboxamide; TZ) is an oral alkylating drug used for the treatment of primary brain tumors (6, 7). The temozolomide signal is saturated in the method for the determination of temozolomide related substances used for the assessment of the chemical purity of temozolomide samples manufactured by Pharmaceutical Research Institute (PRI), which imposed the necessity of using separate methods for the temozolomide API assay and purity determination (2). The aim of the study was to apply the i-DReC data analysis function of the LabSolutions software to the determination of temozolomide assay using a method for the chemical purity determination. It was possible in spite of the temozolomide signal being saturated.