Livia Manna

RP-HPLC study of the degradation of diclofenac and piroxicam in the presence of hydroxyl radicals

The effect of hydroxyl radical attack on two non-steroidal anti-inflammatory drugs (NSAIDs) was studied in vitro. Diclofenac and piroxicam were analysed by RP-HPLC after reaction with OH* free radicals to detect newly formed oxidation and/or degradation products. OH* free radicals were obtained by means of ferrous sulphate and ascorbic acid mixtures. During the reaction the mixtures were exposed to irradiation by a tungsten lamp to obtain an increased and more reproducible formation of hydroxyl radicals. The chromatographic profiles showed the formation of several new peaks for both diclofenac and piroxicam due to the presence of a number of degradation/oxidation products formed in the presence of OH* radicals.

An LC method for the simultaneous screening of some common counterfeit and sub-standard antibiotics Validation and uncertainty estimation.

Pharmaceutical counterfeiting is a worldwide public health problem, often under-recognised, especially in developing countries where the percentage of counterfeit and sub-standard medicines is dramatically high. Antibiotics, among the most widespread drugs, have been particularly targeted by counterfeiters. World Health Organization emphasizes the need for development and distribution of screening methods explicitly targeted to counterfeit drugs. In this paper is presented a single method for the simultaneous analysis of some of the most common and counterfeited essential antibiotics: ampicillin, amoxicillin+clavulanic acid, doxycycline, cloxacillin, chloramphenicol. A full validation was performed in terms of linearity, precision, robustness and trueness; an assessment of uncertainty was carried out exploiting these data. A wide linearity range was investigated considering the specific nature of counterfeit and sub-standard drugs, whose content in active substance may be rather far from the declared amount. A large span in robustness parameters was considered and a complete intermediate precision assessment was conducted, envisaging the possibility of transferring the method to quality control laboratories, hopefully in developing countries. Finally, the method was successfully applied to the analysis of antibiotics purchased on the informal market in Chad, among which counterfeit and sub-standard samples were detected.

A liquid chromatographic lon-pairing method for simultaneous determination of benazepril hydrochloride, fosinopril sodium, ramipril and hydrochlorothiazide in pharmaceutical formulations

SummaryA rapid and accurate reversed-phase ion-pairing liquid chromatographic method with UV detection was developed for the simultaneous assay of the angiotensin-converting enzyme inhibitors benazepril hydrochloride, fosinopril sodium and ramipril, and the diuretic hydrochorothiazide.The separation was achieved on a LC-8 (125×4.0 mml.D.; 5μm particle size) column.The mobile phase consisted of 20 mM sodium heptanesulphonate (pH=2.5) and methanol (32:68v/v).Validation of the method showed it to be precise, accurate and linear over the concentration range of analysis with a limit of detection of 1 ng for hydrochorothiazide, 2 ng for ramipril and benazepril and 8 ng for fosinopril.The method developed was applied to the analysis of three different binary commercial formulations.

A Survey on Illegal and Counterfeit Medicines for the Treatment of Erectile Dysfunctions in Italy

INTRODUCTION In developed countries the phenomenon of pharmaceutical counterfeiting is steadily increasing through the illegal and the Internet market. Medicines for the treatment of erectile dysfunctions containing phosphodiesterase type 5 inhibitors (PDE5) are especially prone to falsification. AIMS To obtain evidence of the health risks for patients taking these products and to provide useful information to general practitioners and specialists in sexual medicine. METHODS First the samples were visually inspected and then analyzed to get information about their identity and quality. MAIN OUTCOME MEASURES A survey on the PDE5 medicines analyzed by the Italian official medicines control laboratory between 2005 and 2011 was performed. All the analyzed medicines were gathered from the Italian illegal market (seizures by police forces) or were bought from illegal online pharmacies. Results.  The study revealed that 24% of the analyzed samples were counterfeit and 54% were illegal medicines. In 12% of the cases an intermediate classification (illegal/counterfeit) was assigned. Only 7% of the samples were original. Moreover, the examination of the packaging evidenced potential risks: outer and immediate packaging missing; inconsistency between the carton box and the blister as regards the expiry date and/or the batch number; expiry date or manufacturers name or country missing. CONCLUSIONS In 19% of the samples a potential health risk for patients was identified due to either the presence in the sample of more than one undeclared PDE5(s) or an amount of the active ingredient higher than that declared (up to 190% of the maximum dose) or to the presence of potentially dangerous excipients of non-pharmaceutical origin or quality (e.g., gypsum or non-purified talc).

Amoxicillin sodium-potassium clavulanate: evaluation of gamma radiation induced effects by liquid chromatography on both the individual drugs and their combination.

The effects of gamma irradiation on the stability of potassium clavulanate, amoxicillin sodium and their combination were investigated. A decrease in purity and increase in degradation products up to 30 days after the irradiation were evaluated by reversed phase HPLC. The comparison between unirradiated and irradiated amoxicillin sodium, performed within 24 h following the irradiation process, showed no significant increase in the pre-existing impurities and no evidence of newly induced degradation products. On the contrary, an appreciable increase in the content of some impurities was evidenced 30 days after the irradiation. The chromatographic profile of irradiated potassium clavulanate showed the appearance of one unidentified new product and a slight increase of one pre-existing impurity. No further change in the impurity content was noted 30 days after the irradiation. The amoxicillin sodium-potassium clavulanate combination underwent the same kind of radiation induced degradation as the single compounds.

Development and validation of a reversed-phase liquid chromatographic method for the assay of lidocaine in aqueous humour samples

A simple, fast and reliable reversed-phase liquid chromatographic method was developed for the assay of lidocaine in human aqueous humour samples. The samples were analysed without any preliminary treatment on a C8 column with UV detection at 225 nm. The mobile phase consisted of methanol/sodium dihydrogen phosphate (30 mM) containing sodium pentansulphonate (10 mM) adjusted to pH 2.5 with phosphoric acid (50:50 v/v). Validation of the method showed it to be precise, accurate and linear over the concentration range of analysis with a limit of detection of 0.2 microgml(-1). The limit of quantitation was 2.5 microgml(-1) with a relative standard deviation of 2.5%. Linear regression analysis in the range 2.5-60 microgml(-1) gave correlation coefficients higher than 0.999. No interference from three commonly co-administered drugs was observed. The method developed was applied to the analysis of lidocaine in aqueous humour samples in order to evaluate and compare the efficacy of two different forms of administration of lidocaine for topical anaesthesia in cataract surgery.

Different crystal morphologies arising from different preparation methods of a same polymorphic form may result in different properties of the final materials: the case of diclofenac sodium trihydrate.

Diclofenac sodium is a nonsteroidal anti-inflammatory drug widely used in painful and inflammatory diseases. It can exist in different hydrate phases. Recently the physico-chemical and pharmaceutical properties of a trihydrate form, named DSH3 were reported by the same authors. This short communication discusses how samples of a same polymorphic form can display dissimilar analytical signatures when obtained by different routes. Data from hot-stage microscopy, FT-IR spectroscopy, X-ray powder diffraction (XRDP) and thermal analysis were used to characterise the DSH3 samples prepared by different methods. Through the case study of diclofenac sodium, this work highlights how the method used to prepare a specific crystal modification can generate samples with different morphologies and therefore different properties and physical stability.