title: Determination of azide impurity in sartans using reversed-phase HPLC with UV detection.
abstract: A simple and robust, gradient HPLC method was developed for determination of azide ppm (μgg(-1)) levels in different sartans (irbesartan, candesartan, valsartan). The sartan was dissolved in 0.1M NaOH. Then pH was adjusted to 4.5 with 20% H3PO4 followed by dilution with water. Precipitated API was removed by filtration using 0.45μm membrane PVDF (Polyvinylidene Fluoride) membrane filter, and supernatant was analyzed by gradient elution HPLC at room temperature with Hydro RP HPLC 250×4.6mm, 4μm column and UV detection at 205nm. The best sensitivity was achieved by UV detection cell with 60mm optical path length: LOD 0.17μgg(-1) and LOQ 0.84μgg(-1) for azide. The USP requirement for maximum azide content in irbesartan is 10μgg(-1). The analytical method was validated as per International Conference on Harmonization (ICH) guidelines with respect to system precision, intraday precision (repeatability), intermediate precision (ruggedness), linearity, quantitation limit, detection limit, accuracy, standard and sample solution stability, robustness and selectivity/specificity. The method was linear in the range from LOQ (0.84μgg(-1)) to 101μgg(-1) of azide. The correlation coefficient was 0.9999 and bias on y-axis for 84μgg(-1) test concentration was 0.33%. The accuracy of the method was established based on the recovery obtained between 94.0% and 103.0% for azide. Standard and sample solutions were stable for at least 48h at room temperature and in refrigerator. The method was found to be robust for variation in column temperature (±5°C) and mobile phase flow rate (±0.2mLmin(-1)) and selective for anions such as bromide, nitrate, nitrite, formate and acetate.
authors.affiliation: Center for Validation Technologies and Analytics, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Gričar
authors.affiliation: Center for Validation Technologies and Analytics, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia. Electronic address: samo.andrensek@ki.si.
authors.forename: Samo
authors.initials: S
authors.lastname: Andrenšek
mesh_terms: D001386:Azides / Q000032:analysis*; D001562:Benzimidazoles / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077405:Irbesartan; D057230:Limit of Detection; D012015:Reference Standards; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013777:Tetrazoles / Q000737:chemistry*; D000068756:Valsartan / Q000737:chemistry*
chemical_list: D001386:Azides; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000068756:Valsartan; D000077405:Irbesartan; C081643:candesartan
keywords: Azide; Candesartan; Genotoxic impurity; HPLC-UV; Irbesartan; Sartans; Valsartan