Electroanalytical determination of codeine in pharmaceutical preparations

A square wave voltammetric (SWV) method and a flow injection analysis systemwi th electrochemical detection (FIA-EC) using a glassy carbon electrode were evaluated for the determination of codeine in pharmaceutical preparations. The interference of several compounds, such as acetaminophen,guaiacol, parabens, ephedrine, acetylsalicylic acid and caffeine, that usually appear associated with codeine pharmaceutical preparations was studied. It was verified that these electroanalytical methods could not be used with acetaminophen present in the formulations and that with guaiacol, parabens or ephedrine present the use of the FIA-EC system was impracticable. A detection limit of 5 µmol L- 1 and a linear calibration range from 40 to 140 µmol L- 1 was obtained with the SWV method. For the flow injection analysis procedure a linear calibration range was obtained from 7 to 50 µmol L- 1 with a detection limit of 3 µmol L- 1 and the FIA-EC systemallowed a sampling rate of 115 samples per hour. The results obtained by the two methods, SWV and FIA-EC, were compared with those obtained using reference methods and demonstrated good agreement, with relative deviations lower than 4%.

N.C.R.F. 3: adopção pela primeira vez das Normas Contabilísticas e de Relato Financeiro

Dissertação para obtenção do Grau de Mestre em Auditoria

O Contributo do sistema SAP R/3 no controlo interno na REFER

Dissertação apresentada ao Instituto Superior de Contabilidade para a obtenção do Grau de Mestre em Auditoria Orientador: Mestre Agostinho Sousa Pinto

Mergers and acquisitions as strategies of business expansion in the pharmaceutical industry

Introduction: The present paper deals with the issue of the increasing usage of corporation mergers and acquisitions strategies within pharmaceutical industry environment. The aim is to identify the triggers of such business phenomenon and the immediate impact on the financial outcome of two powerful biopharmaceutical corporations: Pfizer and GlaxoSmithKline, which have been sampled due to their successful approach of the tactics in question. Materials and Methods: In order to create an overview of the development steps through mergers and acquisitions, the historical data of the two corporations has been consulted, from their official websites. The most relevant events were then associated with adequate information from the financial reports and statements of the two corporations indulged by web-based financial data providers. Results and Discussions: In the past few decades Pfizer and GlaxoSmithKline have purchased or merged with various companies in order to monopolize new markets, diversify products and services portfolios, survive and surpass competitors. The consequences proved to be positive although this approach implies certain capital availability. Conclusions: Results reveal the fact that, as far as the two sampled companies are concerned, acquisitions and mergers are reactions at the pressure of the highly competitive environment. Moreover, the continuous diversification of the market’s needs is also a consistent motive. However, the prevalence and the eminence of mergers and acquisition strategies are conditioned by the tender offer, the announcer’s caliber, research and development status and further other factors determined by the internal and external actors of the market.

Feedback regarding students initial pharmaceutical internship from the University of Medicine and Pharmacy, Cluj-Napoca

Introduction/Aims: The purpose of the study is to evaluate the perception of the organization, the development and the evaluation of the initial stage in the internship of students, in order to improve these activities and to establish the adequate objectives in accordance with the changes concerning the concept of modern pharmacy. Materials and methods: An online survey was made using Google Docs ® -Create Form extension. All results were accumulated and computed using Microsoft Excel ®. The questionnaire consisted of 11 questions, structured on several levels: the objectives and how they can be achieved, internship organization, the internship training (effective participation in specific activities and integration in the pharmaceutical activity), the assessment, the profile of tutor / pharmacy. The questionnaire was completed by students from the Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Haţieganu" Cluj Napoca, Romania. Results and discussions. The study was conducted on 308 students (60% of all students from the study years II-IV. 90% of the respondents had actually participated in the internship, whilst 10% only formally participated in this activity. The main responsibilities of the students were: storage and reception of pharmaceutical products (94%, respectively 79%) and working with the receipts (57%). Most of the students appreciate that they were integrated into the work in the pharmacy, this being due largely pharmacist tutor, who expressed interest and ability in mentoring activities. They appreciated that the role of tutor requires 3-5 years of professional experience. In terms of the internship objectives, these should aim at applying the knowledge gained until the graduation year, but also familiarization with activities which might turn into applications for the coming years. 43% of students believe that only 25% of the theoretical knowledge was useful during the internship. 90 % of the total questioned considered useful to develop a practice guideline adapted to the year of study. Conclusions. The professional training of the future pharmacist’s students depends largely on experience gained by students during the internship activity. Feed-back from the students’ shows that they are aware of the usefulness of the internship, but believe the objectives must be updated and a better correlation between work in pharmacy and theoretical knowledge has to be made. A first step is to develop a practical guide adapted to each year of study. The involvement of the tutor pharmacist is also essential to the success of this activity

Development of electrochemical methods for determination of tramadol - analytical application to pharmaceutical dosage forms

A square-wave voltammetric (SWV) method and a flow injection analysis system with amperometric detection were developed for the determination of tramadol hydrochloride. The SWV method enables the determination of tramadol over the concentration range of 15-75 µM with a detection limit of 2.2 µM. Tramadol could be determined in concentrations between 9 and 50 µM at a sampling rate of 90 h-1, with a detection limit of 1.7 µM using the flow injection system. The electrochemical methods developed were successfully applied to the determination of tramadol in pharmaceutical dosage forms, without any pre-treatment of the samples. Recovery trials were performed to assess the accuracy of the results; the values were between 97 and 102% for both methods.

Direct electroanalytical determination of fluvastatin in a pharmaceutical dosage form: batch and flow analysis

The reduction of luvastatin (FLV) at a hanging mercury-drop electrode (HMDE) was studied by square-wave adsorptive-stripping voltammetry (SWAdSV). FLV can be accumulated and reduced at the electrode, with a maximum peak current intensity at a potential of approximately 1.26V vs. AgCl=Ag, in an aqueous electrolyte solution of pH 5.25. The method shows linearity between peak current intensity and FLV concentration between 1.0 10 8 and 2.7 10 6 mol L 1. Limits of detection (LOD) and quantification (LOQ) were found to be 9.9 10 9 mol L 1 and 3.3 10 8 mol L 1, respectively. Furthermore, FLV oxidation at a glassy carbon electrode surface was used for its hydrodynamic monitoring by amperometric detection in a flow-injection system. The amperometric signal was linear with FLV concentration over the range 1.0 10 6 to 1.0 10 5 mol L 1, with an LOD of 2.4 10 7 mol L 1 and an LOQ of 8.0 10 7 mol L 1. A sample rate of 50 injections per hour was achieved. Both methods were validated and showed to be precise and accurate, being satisfactorily applied to the determination of FLV in a commercial pharmaceutical.

Electrochemical determination of citalopram by adsorptive stripping voltammetry–determination in pharmaceutical products

The electrochemical behavior of citalopram was studied by square-wave and square-wave adsorptive-stripping voltammetry (SWAdSV). Citalopram can be reduced and accumulated at a mercury drop electrode, with a maximum peak current intensity being obtained at a potential of approximately -1.25V vs. AgCl/Ag, in an aqueous electrolyte solution of pH 12. A SWAdSV method has been developed for the determination of citalopram in pharmaceutical preparations. The method shows a linear range between 1.0x10-7 and 2.0x10-6 mol L-1 with a limit of detection of 5x10-8 mol L-1 for an accumulation time of 30 s. The precision of the method was evaluated by assessing the repeatability and intermediate precision, achieving good relative standard deviations in all cases (≤2.3%). The proposed method was applied to the determination of citalopram in five pharmaceutical products and the results obtained are in good agreement with the labeled values.

Flow injection electrochemical determination of apomorphine

Few analytical methods are currently available for determination of apomorphine, the active substance of a new oral formulation used in the treatment of erectile dysfunction. In this way a flow injection electrochemical method (FIA-EC) was developed for its quantification and applied to pharmaceutical dosage forms. Based in previous findings regarding the stability of apomorphine in borate buffer and after optimization of several analytical parameters a single channel flow injection manifold was set up that enables the determination of this drug over the concentration range of 3 to 16 µmol L-1 with a detection limit of 0.5 µmol L-1 at a sampling rateof 90 h-1. The simplicity and rapidity of the FIA-EC method used, its reproducibility and sensitivity make it suitable for quality control of pharmaceutical preparations of apomorphine intended for clinical use and research.

Citrate selective electrodes for the flow injection analysis of soft drinks, beers and pharmaceutical products

Aiming the establishment of simple and accurate readings of citric acid (CA) in complex samples, citrate (CIT) selective electrodes with tubular configuration and polymeric membranes plus a quaternary ammonium ion exchanger were constructed. Several selective membranes were prepared for this purpose, having distinct mediator solvents (with quite different polarities) and, in some cases, p-tert-octylphenol (TOP) as additive. The latter was used regarding a possible increase in selectivity. The general working characteristics of all prepared electrodes were evaluated in a low dispersion flow injection analysis (FIA) manifold by injecting 500µl of citrate standard solutions into an ionic strength (IS) adjuster carrier (10−2 mol l−1) flowing at 3ml min−1. Good potentiometric response, with an average slope and a repeatability of 61.9mV per decade and ±0.8%, respectively, resulted from selective membranes comprising additive and bis(2-ethylhexyl)sebacate (bEHS) as mediator solvent. The same membranes conducted as well to the best selectivity characteristics, assessed by the separated solutions method and for several chemical species, such as chloride, nitrate, ascorbate, glucose, fructose and sucrose. Pharmaceutical preparations, soft drinks and beers were analyzed under conditions that enabled simultaneous pH and ionic strength adjustment (pH = 3.2; ionic strength = 10−2 mol l−1), and the attained results agreed well with the used reference method (relative error < 4%). The above experimental conditions promoted a significant increase in sensitivity of the potentiometric response, with a supra-Nernstian slope of 80.2mV per decade, and allowed the analysis of about 90 samples per hour, with a relative standard deviation <1.0%.

Electrochemical determination of dihydrocodeine in pharmaceuticals

Two analytical methods for the quality control of dihydrocodeine in commercial pharmaceutical formulations have been developed and compared with reference methods: a square wave voltammetric (SWV) method and a flow injection analysis system with electrochemical detection (FIA-EC). The electrochemical methods proposed were successfully applied to the determination of dihydrocodeine in pharmaceutical tablets and in oral solutions. These methods do not require any pretreatment of the samples, the formulation only being dissolved in a suitable electrolyte. Validation of the methods showed it to be precise, accurate and linear over the concentration range of analysis. The automatic procedure based on a flow injection analysis manifold allows a sampling rate of 115 determinations per hour.

Electroanalytical study of the antidepressant sertraline

Aflowinjection squarewave cathodic stripping voltammetric method has been developed for the determination of sertraline in a pharmaceutical preparation. The method shows linearity between peak current intensity and sertraline concentration for the interval between 0.20×10−6 and 1.20×10−6 mol L−1. Limits of detection and quantification were found to be 1.5×10−7 and 5.0×10−7 mol L−1, respectively. Up to 70 samples per hour can be analysed with a good precision (R.S.D. = 2.5%). The proposed method was successfully applied to the determination of sertraline in a commercial product. In the voltammetric determination of sertraline in flow, a high sample rate is obtained at reduced costs, opening the possibility to compete with the chromatographic methods generally used for this analysis.

Flow injection potentiometric determination of chlorpromazine

New chlorpromazine selective electrodes with a tubular arrangement and no internal reference solution are proposed. Selective membranes are of poly(vinyl chloride) (PVC) with the tetraphenylborate•chlorpromazine (TPB•CPZ) ion-exchanger dissolved in o-nitrophenyl octyl ether (oNPOE). Analytical features of the electrodes were evaluated on a single-channel flow assembly having 500 µl injection volumes and flow-rates of 4.5 ml min−1. For a carrier solution of 3.3×10−3Min sodium sulphate, Nernstian responsewas observed over the concentration range 1.0×10−5 to 1.0×10−2 M. Average slopes were about 59mVdecade−1 and squared correlation coefficients were >0.9984. Slight hiper-Nernstian behaviour was observed in buffer solutions of 4.4 pH; average slopes were of 62.06mVdecade−1. The electrode displayed a good selectivity for CPZ, with respect to, several foreign inorganic and organic species. The selective electrodes were successfully applied to the analysis of pure solutions and pharmaceutical preparations. Proposed method allows the analysis of 84 samples h−1, producing wastewaters of low toxicity. The proposed method offers the advantage of simplicity, accuracy, applicability to coloured and turbid samples, and automation feasibility.