ABSTRACT
The objective of this work was the development and validation of atomic absorption spectrometric (AAS) methods for the determination of residual active pharmaceutical ingredients (API) in rinse samples for cleaning validation. AAS as an indirect method for the determination of API in rinse samples can be applied when it is in the form of salt with metal ions or when the metal ion is a part of the API's structure. The electrothermal AAS methods (aqueous and ethanol medium) for the determination of magnesium in esomeprazole magnesium and the flame AAS method for the determination of lithium in lithium carbonate in rinse samples were developed. Various combinations of solvents were tested and a combination of 1% aqueous or ethanol solution of nitric acid for esomeprazole magnesium and 0.1% aqueous solution of nitric acid for lithium carbonate were found to be the most suitable. The atomization conditions in the graphite furnace and in the flame were carefully studied to avoid losses of analyte and to achieve suitable sensitivity. The cleaning verification methods were validated with respect to accuracy, precision, linearity, limit of detection, and quantification. In all the cases, the limits of detection were at the microgram level. The methods were successfully applied for the determination of esomeprazole magnesium and lithium carbonate in rinse samples from cleaning procedures.
Subject(s)
Equipment Contamination/prevention & control , Esomeprazole/analysis , Lithium Carbonate/analysis , Pharmaceutical Preparations/analysis , Spectrophotometry, Atomic/methods , Anti-Ulcer Agents/analysis , Anti-Ulcer Agents/chemistry , Antimanic Agents/analysis , Antimanic Agents/chemistry , Esomeprazole/chemistry , Ethanol/chemistry , Linear Models , Lithium/analysis , Lithium Carbonate/chemistry , Magnesium/analysis , Reproducibility of Results , Water/chemistryABSTRACT
An electrothermal atomic absorption spectrometric procedure for the determination of nickel in active pharmaceutical ingredients was developed. Since the recoveries of nickel by the direct dissolution of samples in diluted nitric acid were low and caused errors in the determination of Ni in pharmaceutical samples, different approaches for sample pre-treatment were examined. It was found that the microwave digestion was the most suitable way for sample preparation. Various combinations of digestion agents and different microwave conditions were tested. The combination of nitric acid and hydrogen peroxide was found to be the most appropriate. The validity of the method was evaluated by recovery studies of spiked samples and by the comparison of the results obtained by inductively coupled plasma mass spectrometry (ICP-MS). The recovery ranged from 87.5 to 104.0% and a good agreement was achieved between both methods. The detection limit and the limit of quantification were 0.6 and 2.1 µg g-1 respectively. The precision of the method was confirmed by the determination of Ni in the spiked samples and was below 4%, expressed in terms of a relative standard deviation. The method was applied to the determination of nickel in production samples of active pharmaceutical ingredients and intermediates.
