Fávero Reisdorfer Paula

Determination of toxic elements in tricyclic active pharmaceutical ingredients by ICP-MS: a critical study of digestion methods

The determination of As, Cd, Hg and Pb in tricyclic active pharmaceutical ingredients (APIs) was performed by ICP-MS after digestion by both combustion and wet digestion methods. Carbamazepine was digested using the dry ashing method recommended in United States Pharmacopeia 35th edition and significant losses of analytes were observed in recovery tests (38.0 ± 8.9, 99.5 ± 7.1, and 89.4 ± 6.3% of recovery for As, Cd and Pb, respectively). Mercury was completely lost by volatilization during digestion. The digestion of carbamazepine, amitriptyline hydrochloride and imipramine hydrochloride by microwave-assisted wet digestion in closed vessels (MW-AD) was not effective and a yellow-orange solid residue was observed for all substances. 1H NMR of the carbamazepine residue indicated the nitration of carbamazepine aromatic rings forming stable nitro compounds. High pressure asher digestion systems were also used and solid residues were observed for carbamazepine and amitriptyline hydrochloride even under drastic digestion conditions (280 °C, 120 min). A complete digestion of all substances was obtained only by the use of high temperature and long time of digestion and reduction of sample mass to 0.08 g (320 °C, 180 min). The microwave-induced combustion (MIC) method for digestion of tricyclic APIs allowed the digestion of 0.5 g of all substances with high efficiency (RCC lower than 1%) using diluted nitric acid as absorbing solution (7 mol l−1). The recoveries using this method were between 94 and 103% for the evaluated elements. The low RCC and acidity of digests obtained using MIC allowed the compatibility with ICP-MS and makes MIC a promising alternative as a sample preparation method for subsequent determination of toxic elements in APIs by ICP-MS.

Determination of total arsenic by batch hydride generation atomic absorption spectrometry in injectable drugs containing high levels of Sb(V) as N-methylglucamine antimonate

Abstract A procedure for the determination of arsenic by batch hydride generation atomic absorption spectrometry (HG AAS) in commercial samples of injectable drugs, containing high concentrations of Sb(V), is described. The procedure is based on the complexing effect for Sb of citric, oxalic and acetic acids as reaction media. Aqua regia was used for sample digestion prior to As determination by HG AAS. The following experimental conditions for the determination of total As, as As(V), were evaluated: the acid medium and its concentration, sodium tetrahydroborate concentration, purge time, and influence of the different oxidation states of As. The effect of the delay time after mixing of sample and acid solution was also studied. Optimized conditions were: 10% (m/v) citric acid, 1.5% (m/v) sodium tetrahydroborate solution and 30 s for purge time. A delay time of 1 h was required after the digested sample had been mixed with citric acid, before As determination could be carried out. No interference on As(III) and As(V) signals was observed in the presence of up to 1 mg Sb(V). The tolerance limits for Ni(II), Cu(II) and Pb(II) were 1 mg, 100 μg and 100 μg, respectively. Recovery tests for As(III) and As(V) resulted in values between 97 and 101%. Characteristic mass and detection limit (3σ), using the recommended conditions, were 0.52 and 0.8 ng, respectively, for total As.

Stability Study of Finasteride: Stability-Indicating LC Method, In Silico and LC–ESI-MS Analysis of Major Degradation Product, and an In Vitro Biological Safety Study

Stability studies of the pharmaceutically important compound finasteride were conducted in order to evaluate decomposition of the drug under forced degradation conditions. A simple stability-indicating liquid chromatography method was developed and validated for the evaluation of finasteride and degradation products formed in pharmaceutical preparations and the raw material. Isocratic LC separation was achieved on a C18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 2.8 with triethylamine (10% v/v) and acetonitrile (52:48 v/v), with a flow rate of 1.0 mL min-1. The alkaline degradation kinetics of the drug were also evaluated and could be best described as second-order kinetics under the experimental conditions applied for the tablets and raw material. Based on in silico studies and molecular weight confirmation, a comprehensive degradation pathway for the drug and the identity of its major product could be suggested without complicated isolation or purification processes. Furthermore, a biological safety study was performed to evaluate the effect of the degraded sample in relation to the intact molecule. The results showed that the degraded sample affected the cell proliferation. Therefore, these studies show that special care must be taken during the manipulation, manufacture and storage of this pharmaceutical drug.