ABSTRACT
Quantification of impurities in drug substances and dosage forms using HPLC assays with UV detection is often done by comparison to a standard of the drug itself. Depending on the spectra of the compounds involved, small changes in wavelength may cause response factors to vary from day to day and instrument to instrument. Lack of assay ruggedness with respect to wavelength can lead to poor reproducibility of results. Response factor ruggedness was investigated for potential impurities in LY297802 tartrate, a potent muscarinic agonist. The UV responses of some impurities at 280 nm, the analytical detection wavelength, differ from that of the parent and change significantly with small shifts in wavelength. The ruggedness of response factors was examined on a single detector and among several different detectors. Results varied significantly among the different detectors. The UV spectra of the impurities could be used to predict the effect of wavelength on ruggedness of response. A wavelength system suitability sample is proposed as a way to overcome variability due to small differences in detector wavelength.
Subject(s)
Chemistry, Pharmaceutical/methods , Cholinergic Agents/chemistry , Chromatography, High Pressure Liquid/methods , Drug Contamination , Pharmaceutical Preparations/chemistry , Thiadiazoles/chemistry , Linear Models , Reproducibility of Results , Spectrophotometry, UltravioletABSTRACT
This vapour-phase acid decomposition of small biological samples (50-165 mg) and concurrent purification of the reagent acid were achieved in a mini-quartz sample holder inserted in a commercial high-pressure digestion vessel. A 3.1 ml volume sample contained was developed to hold the sample and to maximize the successful decomposition of a variety of biological samples. When biological standard reference materials were digested at 230 degrees C and 122 bar (1770 psi), the residual carbon content in the digested samples was less than 1.8 +/- 0.1%. Inductively coupled plasma atomic emission spectrometric analysis of the digested materials for C, Ca, Cu, Cd, Fe, Mg, Mn and Zn provided good recoveries and low reagent blank values and demonstrated complete matrix decomposition.
