Preparo de amostras e análise elementar de produtos farmacêuticos
Abstract
The medicine manufacture process may cause the final product contamination with
metallic residues to the detriment of human healthy. Aiming to regulate the
pharmaceutical production and establish standards of final products quality,
organizations such as the USP, EMA and ICH established regulations governing
maximum exposure to target elements, including some metals that are known to be
toxic to human health. Other elements, despite its essentiality in certain
concentrations, require exposure control. Regularly a sample to be measured by ICP
techniques requires its conversion to a representative solution, usually involving
microwave-assisted acid digestion. Once decomposed, the elemental analysis is done
using inductively coupled plasma techniques. This study aims to establish a general
method of sample preparation and elemental analysis of drug samples (excipients,
continuous use drugs, multivitamins, multiminerals and natural products), in order to
meet the demands of the pharmaceutical industry. In this sense, sample preparation
was based on microwave assisted acid digestion using the following reagents: nitric
acid, hydrochloric acid and hydrogen peroxide. The established procedure involves a
41 min heating program with a maximum temperature of 210 oC. The efficiency of
digestion was assessed by determination of dissolved organic carbon. Best digestions
were reached using 5 ml of inverted aqua regia for 500 mg of sample. The elemental
analysis techniques used were ICP OES and ICP-MS. In both cases, analytical
calibration curves were built based on the J value, established by USP, which takes
into account the permitted daily exposure to the target element, the maximum daily
dose of medicament and the sample dilution factor. Both techniques were suitable for
metal impurities determination. For ICP OES recoveries were close to 100% for most
analytes in all tested samples. For ICP-MS, despite being within the range from 70 to
150% set by USP, recoveries still require further evaluation.