Development and validation of a stability-indicating UPLC method for rosuvastatin and its related impurities in pharmaceutical dosage forms

The present work describes a novel stability-indicating reversed-phase ultra performance liquid chromatography method for the separation and quantification of rosuvastatin (RSV) and its related impurities in the pharmaceutical dosage forms under forced degradation conditions. An unknown degradation impurity detected in the acid degradation was identified by using quadrupole time-of-flight mass spectrometry. The chromatographic separation was carried out on C-18 column (100 x 2.1 mm, 1.7 μm) using isocratic elution with methanol and 0.1% trifluoroacetic acid (50:50). The total run time was 12 min within which RSV as well as all related impurities and degradation products were separated. The developed method was validated for RSV and related impurities in pharmaceutical dosage forms.

A sensitive and robust lc-ms/ms method with monolithic column and electrospray ionization for the quantitation of efavirenz in human plasma: application to a bioequivalence study

An LC-MS/MS method has been developed for the determination of efavirenz (EFZ) in human plasma using hydrochlorothiazide as internal standard (I.S.). An ESI negative mode with multiple reaction-monitoring was used monitoring the transitions m/z 313.88→69.24 (EFZ) and 296.02→204.76 (I.S.). Samples were extracted using liquid-liquid extraction. The total run time was 2.0 min. The separation was achieved with HPLC-RP using a monolithic column. The assay was linear in the concentration range of 100 - 5000 ng mL-1. The mean recovery was 83%. Intra- and inter-day precision were < 9.5% and < 8.9%, respectively and accuracy was in the range ± 8.33%. The method was successfully applied to a bioequivalence study.

Determinação rápida de oseltamivir em cápsulas por cromatografia líquida de ultraeficiência com detector por arranjo de diodos

A simple and rapid ultra-performance liquid chromatographic method for determination of oseltamivir in capsules was developed and validated. The mobile phase consisted of 5 mmol/L triethylammonium buffer (pH 3.0) and acetonitrile (70:30, v/v). Separation was performed in a Hypersil Gold® column, with octylsilil as stationary phase (100 x 2.1 mm, p.d. 1.9 µm). Chromatography run time was 1.2 min. The method presented adequate specificity, linearity, precision, ruggedness and accuracy and was adequate for determination of oseltamivir in capsules.

Determinação rápida de fármacos básicos em plasma por cromatografia a gás com detector de nitrogênio e fósforo

A simple and fast method for determination of 40 basic drugs in human plasma employing gas-chromatography with nitrogen-phosphorus detection was developed and validated. Drugs were extracted from 800 µL of plasma with 250 µL of butyl acetate at basic pH. Aliquots of the organic extract were directly injected on a column with methylsilicone stationary phase. Total chromatographic run time was 25 min. All compounds were detected in concentrations ranging from therapeutic to toxic levels, with intermediate precision CV% below 11.2 and accuracy in the range of 92-114%.

Determinação simultânea de topiramato, carbamazepina, fenitoína e fenobarbital em plasma empregando cromatografia a gás com detector de nitrogênio e fósforo

Topiramate and the other frequently co-administered antiepileptic drugs carbamazepine, phenytoin and phenobarbital were determined in 100 µL plasma samples by gas chromatography with nitrogen phosphorus detection (GC-NPD), after a one-step liquid-liquid extraction with ethyl acetate, followed by flash methylation with trimethylphenylammonium hydroxide. Total chromatographic run time was 12.5 min. Intra-assay and inter-assay precision was 2.5-7.3% and 1.6-5.2%, respectively. Accuracy was 100.1-104.2%. The limit of quantitation was 1 µg mL-1 for all analytes, proving suitable for routine application in therapeutic drug monitoring of antiepileptic drugs.

Determinação simultânea de carbamazepina, fenitoína e fenobarbital em sangue seco em papel por cromatografia líquida de alta eficiência

Carbamazepine, phenobarbital and phenytoin were determined in dried blood spots (DBS) by high performance liquid chromatography, after extraction of 8 mm DBS using a mixture of acetonitrile and methanol. Analytes were separated by reversed-phase chromatography, with a run time of 17 minutes. Intra-assay and inter-assay precisions were in the 5.3 to 8.4% and 3.3 to 5.2% ranges, respectively. Accuracy was in the 98.8 to 104.3% range. The method had sensitivity to detect all analytes at levels below minimum therapeutic concentrations. The analytes were stable at 4 ºC and room temperature for up to 12 days and at 45 ºC for 9 days. The method was applied to 14 paired clinical samples of blood serum and DBS.

FAST GC-FID METHOD FOR MONITORING ACIDIC AND BASIC CATALYTIC TRANSESTERIFICATION REACTIONS IN VEGETABLE OILS TO METHYL ESTER BIODIESEL PREPARATION

A fast gas chromatography with a flame ionisation detector (GC-FID) method for the simultaneous analysis of methyl palmitate (C16:0), stearate (C18:0), oleate (C18:1), linoleate (C18:2) and linolenate (C18:3) in biodiesel samples was proposed. The analysis was conducted in a customised ionic-liquid stationary-phase capillary, SLB-IL 111, with a length of 14 m, an internal diameter of 0.10 mm, a film thickness of 0.08 µm and operated isothermally at 160 °C using hydrogen as the carrier gas at a rate of 50 cm s-1 in run time about 3 min. Once methyl myristate (C14:0) is present lower than 0.5% m/m in real samples it was used as an internal standard. The method was successful applied to monitoring basic and acidic catalysis transesterification reactions of vegetable oils such as soybean, canola, corn, sunflower and those used in frying process.

Web-käyttöliittymän ajonaikainen parametripohjainen luominen

Työssä tutkitaan eri tekniikoita, joilla web-käyttöliittymä voidaan toteuttaa. Tutkituista tekniikoista valitaan työn tavoitteisiin ja rajoitteisiin parhaiten soveltuvat tekniikat, joita käytetään hyväksi luotaessa varsinainen käyttöliittymäkerros olemassa olevalle web-sovellukselle. Varsinaiset käyttöliittymät luodaan automaattisesti työn aikana toteutettavalla käyttöliittymägeneraattorilla, joka käyttää hyväkseen käyttöliittymiä kuvaavia XML-kuvaustiedostoja. Tekniikoista parhaiten tarpeisiimme soveltui AJAX-lähestymistapa, joka mahdollistaa sivun osittaisen päivittämisen ja täten työpöytäsovellusmaisemman käytettävyyden nopeamman sivun päivityksen vuoksi. Käyttöliittymägeneraattorin käyttämät kuvaustiedostot puolestaan mahdollistavat käyttöliittymäkontrollien valmiin mallintamisen yleisessä kontrollikuvaustiedostossa sekä niiden helpon muokkaamisen ja sijoittelun sivu-kohtaisesti. Lisäksi käyttöliittymäkerros sisältää monipuoliset käyttöliittymäkontrollit.

Social tagging within task management

Social tagging evolved in response to a need to tag heterogeneous objects, the automated tagging of which is usually not feasible by current technological means. Social tagging can be used for more flexible competence management within organizations. The profiles of employees can be built in the form of groups of tags, as employees tag each other, based on their familiarity of each other’s expertise. This can serve as a replacement for the more traditional competence management approaches, which usually become outdated due to social and organizational hurdles, and obsolete data. These limitations can be overcome by people tagging, as the information revealed by such tags is usually based on most recent employee interaction and knowledge. Task management as part of personal information management aims at the support of users’ individual task handling. This can include collaborating with other individuals, sharing one’s knowledge, both functional and process-related, and distributing documents and web resources. In this context, Task patterns can be used as templates that collect information and experience around tasks associated to it during run time, facilitating agility. The effective collaboration among contributors necessitates the means to find the appropriate individuals to work with on the task, and this can be made possible by using social tagging to describe individual competencies. The goal of this study is to support finding and tagging people within task management, through the effective exploitation of the work/task context. This involves the utilization of knowledge of the workers’ expertise, nature of the task/task pattern and information available from the documents and web resources attached to the task. Vice versa, task management provides an excellent environment for social tagging due to the task context that already provides suitable tags. The study also aims at assisting users of the task management solution with the collaborative construction of light-weight ontology by inferring semantic relations between tags. The thesis project aims at an implementation of people finding & tagging within the java application for task management that consumes web services, which provide the required ontology for the organization.

Väsymiskestävyyden määritys murtumismekaanisilla särönmallinnusohjelmilla

Tässä työssä tutkitaan Wärtsilä Oyj:n moottorin ja ABB Oy:n generaattorin muodostaman aggregaatin väsymiskestävyyttä lineaarisen murtumismekaniikan avulla. Työn tavoitteena on selvittää ABAQUS/XFEM- ja FRANC3D-ohjelman soveltuvuus kuormitukseltaan ja geometrialtaan vaativan generaattorirungon suunnittelutyökaluksi. Generaattorirungon kuormitukset aiheutuvat aggregaatin käynnin sekä käynnistys- ja sammutusvaiheen aikai-sista syntyvistä värähtelyistä. Tutkimuksessa tarkastellaan generaattorirungon väsymistä käynninaikaisella kuormituksella. Työssä mallinnettiin generaattorirungosta valittu hitsausdetalji alimallinnustekniikalla, jolloin alimallin reunaehdot voitiin määrittää aggregaatille tehdyn vastelaskennan perus-teella. Alimallista tutkittiin kahta erilaista hitsiliitostyyppiä, joihin mallinnettiin XFEM- ja FRANC3D-ohjelmilla erikokoisia säröjä hitsiliitosten rajaviivalle sekä juuren puolelle. Tutkittavilla ohjelmilla saatujen jännitysintensiteettikertoimien avulla säröille voitiin las-kea ekvivalentti jännitysintensiteettikerroin, jota verrattiin kokeellisesti saatuun jännitysin-tensiteettikertoimen kynnysarvoon. XFEM- ja FRANC3D-ohjelmia vertailtiin käytön helppouden, tulosten tarkkuuden sekä laskenta-aikojen perusteella. Käytettävyyden ja laskenta-aikojen perusteella XFEM-ohjelma soveltui paremmin käytettäväksi teollisuudessa suunnittelu- ja kehitystyön apu-työkaluna. FRANC3D taas antoi XFEM-ohjelmaa luotettavampia tuloksia, mutta laskenta-ajat olivat moninkertaiset.

On Energy Efficient Computing Platforms

In accordance with the Moore's law, the increasing number of on-chip integrated transistors has enabled modern computing platforms with not only higher processing power but also more affordable prices. As a result, these platforms, including portable devices, work stations and data centres, are becoming an inevitable part of the human society. However, with the demand for portability and raising cost of power, energy efficiency has emerged to be a major concern for modern computing platforms. As the complexity of on-chip systems increases, Network-on-Chip (NoC) has been proved as an efficient communication architecture which can further improve system performances and scalability while reducing the design cost. Therefore, in this thesis, we study and propose energy optimization approaches based on NoC architecture, with special focuses on the following aspects. As the architectural trend of future computing platforms, 3D systems have many bene ts including higher integration density, smaller footprint, heterogeneous integration, etc. Moreover, 3D technology can signi cantly improve the network communication and effectively avoid long wirings, and therefore, provide higher system performance and energy efficiency. With the dynamic nature of on-chip communication in large scale NoC based systems, run-time system optimization is of crucial importance in order to achieve higher system reliability and essentially energy efficiency. In this thesis, we propose an agent based system design approach where agents are on-chip components which monitor and control system parameters such as supply voltage, operating frequency, etc. With this approach, we have analysed the implementation alternatives for dynamic voltage and frequency scaling and power gating techniques at different granularity, which reduce both dynamic and leakage energy consumption. Topologies, being one of the key factors for NoCs, are also explored for energy saving purpose. A Honeycomb NoC architecture is proposed in this thesis with turn-model based deadlock-free routing algorithms. Our analysis and simulation based evaluation show that Honeycomb NoCs outperform their Mesh based counterparts in terms of network cost, system performance as well as energy efficiency.

Readout architectures for hybrid pixel detector readout chips

The original contribution of this thesis to knowledge are novel digital readout architectures for hybrid pixel readout chips. The thesis presents asynchronous bus-based architecture, a data-node based column architecture and a network-based pixel matrix architecture for data transportation. It is shown that the data-node architecture achieves readout efficiency 99% with half the output rate as a bus-based system. The network-based solution avoids “broken” columns due to some manufacturing errors, and it distributes internal data traffic more evenly across the pixel matrix than column-based architectures. An improvement of > 10% to the efficiency is achieved with uniform and non-uniform hit occupancies. Architectural design has been done using transaction level modeling (TLM) and sequential high-level design techniques for reducing the design and simulation time. It has been possible to simulate tens of column and full chip architectures using the high-level techniques. A decrease of > 10 in run-time is observed using these techniques compared to register transfer level (RTL) design technique. Reduction of 50% for lines-of-code (LoC) for the high-level models compared to the RTL description has been achieved. Two architectures are then demonstrated in two hybrid pixel readout chips. The first chip, Timepix3 has been designed for the Medipix3 collaboration. According to the measurements, it consumes < 1 W/cm^2. It also delivers up to 40 Mhits/s/cm^2 with 10-bit time-over-threshold (ToT) and 18-bit time-of-arrival (ToA) of 1.5625 ns. The chip uses a token-arbitrated, asynchronous two-phase handshake column bus for internal data transfer. It has also been successfully used in a multi-chip particle tracking telescope. The second chip, VeloPix, is a readout chip being designed for the upgrade of Vertex Locator (VELO) of the LHCb experiment at CERN. Based on the simulations, it consumes < 1.5 W/cm^2 while delivering up to 320 Mpackets/s/cm^2, each packet containing up to 8 pixels. VeloPix uses a node-based data fabric for achieving throughput of 13.3 Mpackets/s from the column to the EoC. By combining Monte Carlo physics data with high-level simulations, it has been demonstrated that the architecture meets requirements of the VELO (260 Mpackets/s/cm^2 with efficiency of 99%).

An HPLC-UV method for the measurement of permeability of marker drugs in the Caco-2 cell assay

The Caco-2 cell line has been used as a model to predict the in vitro permeability of the human intestinal barrier. The predictive potential of the assay relies on an appropriate in-house validation of the method. The objective of the present study was to develop a single HPLC-UV method for the identification and quantitation of marker drugs and to determine the suitability of the Caco-2 cell permeability assay. A simple chromatographic method was developed for the simultaneous determination of both passively (propranolol, carbamazepine, acyclovir, and hydrochlorothiazide) and actively transported drugs (vinblastine and verapamil). Separation was achieved on a C18 column with step-gradient elution (acetonitrile and aqueous solution of ammonium acetate, pH 3.0) at a flow rate of 1.0 mL/min and UV detection at 275 nm during the total run time of 35 min. The method was validated and found to be specific, linear, precise, and accurate. This chromatographic system can be readily used on a routine basis and its utilization can be extended to other permeability models. The results obtained in the Caco-2 bi-directional transport experiments confirmed the validity of the assay, given that high and low permeability profiles were identified, and P-glycoprotein functionality was established.

Bank of Canada Records, 1958-1989

The Bank of Canada first introduced Canada Savings Bonds during the First and Second World Wars. At the time, they were known as War Savings Certificates and Victory Bonds and were used to fund the war effort. In 1946, Canada Savings Bonds were used as part of Canada’s Postwar Financing Program. At that time, the government also introduced the sale of bonds through payroll deduction. Canada Savings Bonds proved to be very popular, providing investors with a convenient, flexible and safe investment. Over time the bonds failed to remain competitive with other low-risk investment options, and the high cost of administering the program called into question its relevance. An independent report commissioned by the government in 2004 recommended that the bonds be phased out, however, the government decided to keep the program and make some revisions. As of 2012, Canada Savings Bonds are available exclusively through the payroll savings program, while Canada Premium Bonds (introduced in 1998) are available through financial institutions, dealers and by phone.

A Compiler for the dependently typed language Beluga

Les structures avec des lieurs sont très communes en informatique. Les langages de programmation et les systèmes logiques sont des exemples de structures avec des lieurs. La manipulation de lieurs est délicate, de sorte que l’écriture de programmes qui ma- nipulent ces structures tirerait profit d’un soutien spécifique pour les lieurs. L’environ- nement de programmation Beluga est un exemple d’un tel système. Nous développons et présentons ici un compilateur pour ce système. Parmi les programmes pour lesquels Beluga est spécialement bien adapté, plusieurs peuvent bénéficier d’un compilateur. Par exemple, les programmes pour valider les types (les "type-checkers"), les compilateurs et les interpréteurs tirent profit du soutien spécifique des lieurs et des types dépendants présents dans le langage. Ils nécessitent tous également une exécution efficace, que l’on propose d’obtenir par le biais d’un compilateur. Le but de ce travail est de présenter un nouveau compilateur pour Beluga, qui emploie une représentation interne polyvalente et permet de partager du code entre plusieurs back-ends. Une contribution notable est la compilation du filtrage de Beluga, qui est particulièrement puissante dans ce langage.