Single Laboratory Validation of Measurement Procedures

The aim of this presentation was to stress: the importance of having an adequate level of confidence in the measurement results produced, to clarify that validation provides information on procedure characteristiccs; to indicate that experience and knowledge of analytical chemists are of great importance in the process of validation and to explain what should be considered and how the validation may be carried out. The content of this presentation is: VIM 3 (ISO/IEC Guide 99:2007) and ISO/IEC 17025 definitions, but we keep on VIM 3 in this presentation. Brief overview of validation process by answering questions: what validation is, why it is needed, how we do it the outcome of validation

Adherence to Therapy: A Modern Pharmacotherapeutic Approach

Abstract Medication adherence is a crucial contributor to effective chronic diseases management. On the contrary, poor adherence leads to significant worsening of disease, death, and increased healthcare costs.  Moreover, patient non-adherence is not limited to medications only. It can also take other forms, such as the failure to keep appointments, to follow recommended dietary or other lifestyle changes, and to follow recommended preventive health practices. According to the most recent report of the World Health Organization the global adherence among patients with chronic diseases averages 50 % in developed countries, with rates decreasing as the co-morbidities increase. The rates are lower in developing countries. Over the last decade, extensive research on the efficacy of adherence-enhancing strategies has been done. However, the rates of nonadherence have not changed significantly. One of the most significant improvements has been achieved with the inclusion of the patient in the process of determination of therapy. As a consequence, the term “compliance” was replaced with the term “adherence” seeming to indicate a greater involvement of the patient in the therapy decision making process.  The World Health Organization identified five sets of factors that are important for patients to adhere to the long-term therapeutic regimens. These include: the social and economic factors, the health care team and system, the characteristics of the disease (for example, mental or physical disability), the characteristics of the treatment (for example, number of the medicines prescribed, the frequency of administration and side effects), and patient-related factors. In general, medical adherence is better for drugs that provide symptom relief, as opposed to ones used to treat a generally asymptomatic condition. For example, chronic conditions (such as high blood pressure, hyperlipidemia, diabetes, osteoporosis, and depression) are common diseases characterized with few symptoms and poor adherence, consequently. Additionally, studies have shown that compliance rates decrease when the treatment is long-term, involves multiple medications taken concurrently, several times daily. This problem can be overcome by simplifying the therapeutic regime (for example, use of extended-release formulations and / or fixed-dose combination finished pharmaceutical products). Furthermore, medication side effects remain a significant issue. However, the clinical pharmacists can reduce non-adherence suggesting ways to manage minor side effects or identifying alternative treatments with fewer side effects. Educating patients about disease, importance of treatment or prevention, and consequences if not treated, could be successful strategy in enhancing patient adherence. Finally, the frequent follow-up appointments provide an opportunity to discontinue the medication, change the prescription (e.g., dose, frequency) if needed, and overcome barriers responsible for poor adherence. In conclusion, we should emphasize that a coordinated action from health professionals, researchers and policy makers is needed to achieve progress in this area. Keywords Medication adherence; compliance; chronic disease; comorbidit

Клиничка фармација и фармакотерапија - скрипта

Скриптата ,,Клиничка фармација и фармакотерапија” е наменета првенствено на студентите на студиската програма - магистер по фармација, кои го слушаат предметот Клиничка фармација и фармакотерапија на Факултетот за медицински науки, на Универзитетот ,,Гоце Делчев” во Штип. Текстот е претставен во согласност со наставниот план и програма по клиничка фармација и фармакотерапија, а подготвен со цел да им помогне на студентите во совладување на предвидениот материјал и да им го направи учењето полесно и поинтересно. Со помош на овој текст студентите ќе се запознаат со поимот и дефиницијата за клиничка фармација, главната цел и нивоата на дејствување на клиничките фармацевти, нивната улога и задачи во современиот интегриран здравствен систем. Оваа скрипта ќе им овозможи на студентите да ги прошират своите знаења за интеракциите на лекови и механизмите на нивно настанување, да ги препознаваат лековите со висок потенцијал за појава на интеракции, како и групите пациенти со зголемен ризик за интеракции на лекови. Посебно внимание е посветено на несаканите реакции на лекови, нивната класификација на тип А и тип Б, најважните фактори на предиспозиција, механизмите за нивно настанување, утврдување и следење, како и со системот за известување за несакани реакции на лековите. Во текстот се повторуваат и утврдуваат и најважните поими од областа на клиничката фармакологија, а се воведува и поимот за клиничка фармакокинетика како примена на фармакокинетиката во широк опсег на клинички случаи. Студентите се запознаваат и со основните принципи на фармакоекономијата и управувањето со лекови. Целта на фармакоекономијата е да се постигне оптимален однос помеѓу цената и ефектите на фармацевтските продукти, притоа земајќи ги предвид етичките вредности на фармацијата кои го ставаат „здравјето на пациентот пред економскиот бенефит“. Фармакоекономските методи се користат да им помогнат на пациентите, болниците, осигурителните компании и на здравствените работници во донесувањето на правилна одлука за тоа кои лекови да бидат избрани за терапија. Посебно поглавје во ова учебно помагало е посветено на интерпретација на лабораториските резултати, неопходно за успешно функционирање на клиничките фармацевти. Исто така, во текстот се претставени и препораки за примена на лекови во специфични популациони групи (деца, стари, новороденчиња...), како и примена на лекови кај болни со пореметена функција на работа на бубрег/црн дроб

A Laboratory Experience in Analysis of Seized Medicines in the Republic of Macedonia

A counterfeit medicine is defined as a medicinal product which is manufactured by an illegal manufacturer or deliberately mislabeled with respect to identity of registered product. Once they enter the market, those medicines could pose a serious public health risk in a way that they do not deliver the desired effect and/or their use could lead to unexpected adverse effects, such as: anaphylaxis or developing resistance to the medicinal product. Therefore, fighting the entrance of counterfeit medicines in the country presents a significant national issue and requires a well-organized health system as well as market surveillance regulation. The Department for Medicines Quality Control at the Institute for Public Health of the Republic of Macedonia was actively involved in combating counterfeit drugs. In the period from 2007 – 2013, fourteen samples seized from the Customs of Macedonia were submitted to the Bureau of Medicines (Ministry of Health) to be analyzed in the Department for Medicines Quality Control. The identification and determination of the content of active substances was successfully achieved using laboratory methods from the registration documentation provided by the manufacturers of the licensed finished medicinal products or the internal HPLC methods validated previously and intended for control of the potentially counterfeit products. The most of the seized medicines were in pharmaceutical form of tablet (85.8 %), labeled as “Viagra”, “Cialis” or “Levitra”, and only 7.1 % were undeclared. The 14.2 % of samples were false labeled for the active compound. Regarding to the composition of the seized samples, the results showed that the most frequently identified active substances were those for treatment of erectile dysfunction: sildenafil citrate (50.5 %), tadalafil (21.4 %) and vardenafil hydrochloride trihydrate (7.2 %). The most of the analyzed products contained the active substance (64.3 %) outside the acceptable 95 % to 105 % margin of deviation from the declared value. The assay results for sildenafil citrate in the seized tablets were in range 52.1 % - 70.6 % from the declared content. These deviations verified the suspicion of counterfeit. However, for definite confirmation, more discriminating analytical techniques are needed, such as the near infrared spectroscopy (NIR) and/or mass spectrometry (MS). Additionally, the limited resource of reference standards in national quality control laboratories requires more extensive collaboration with international organizations

Development of New Methods of Food Analysis in the frame of METROFOOD-RI – Infrastructure for Promoting Metrology in Food and Nutrition

METROFOOD-RI – Infrastructure for Promoting Metrology in Food and Nutrition – is a pan-European Research Infrastructure as a network of 18 European Countries aimed to promote metrology in food and nutrition. Two Macedonian Institutions: Institute of Public Health and Faculty of Agricultural Sciences and Food recognised as Institutions dealing with food quality and safety are involved in this Infrastructure. METROFOOD-RI mission is to enhance quality and reliability of measurement results, development of new methodology of food analysis that will reduce the costs of monitoring and increase the possibilities for the control of food quality. The enforcement of the Metrological Infrastructure and the improvement of Quality of Chemical Measurements will significantly benefit the Society in the whole. For the Citizens the systems for tracking the food from producer to consumer, monitoring of environmental conditions, and the system for determining the geographical origin of food will provide a comprehensive system that will fulfil buyer's wishes and needs. During the early stage Pro-metrofood grant agreement n°. 739568 (H2020 INFRADEV-02-2016), method development for fatty acids analysis and their determination in the rice flour was performed by the Beneficiary - Institute of Public Health. Now METROFOOD - Preparatory Phase (PP) is on-going project that has received funding from the European Union’s Horizon 2020 under grant agreement 871083

Клиничка фармакологија (скрипта)

Скриптата „Клиничка фармакологија“ е наменета првенствено за студентите на студиските програми по Фармација и Општа медицина кои го слушаат предметот Клиничка фармакологија на Факултетот за медицински науки при Универзитетот „Гоце Делчев“ во Штип. Со помош на овој текст студентите ќе се запознаат со поимот и дефиницијата за Клиничка фармакологија, улогата и задачите во современиот интегриран здравствен систем. Оваа скрипта ќе им овозможи на студентите да ги прошират своите знаења за интеракциите на лековите и несаканите дејства на лековите, да ги препознаваат лековите со висок потенцијал за појава на интеракции, како и групите пациенти со зголемен ризик за интеракции на лековите. Во текстот се повторуваат и се утврдуваат и најважните поими од областа на Клиничката фармакологија, посебно фармакокинетиката и патологијата како услов за корекција на дозата на лековите во широк опсег на клинички случаи. Студентите ќе се запознаат со начинот на препишување на лекови како кај општата популација така и кај одделни патолошки состојби (бубрежна и хепатална инсуфициенција) и секако корекциите на дозирањето кои треба да се извршат во согласност со физиолошките промени кои настануваат во текот на стареењето. Посебно се обрнува внимание на препишувањето на лекови во текот на бременоста и лактацијата, како и кај мали деца. Посебно поглавје во ова учебно помагало е посветено на интеракциите на лекови, јатрогените болести и терапијата на болк

Electrochemical Evaluation of the Synergistic Effect of the Antioxidant Activity of Capsaicin and Other Bioactive Compounds in Capsicum sp. Extracts

The redox features of capsaicin and Capsicum sp. fruit extracts (hot peppers extracts) have been studied at glassy carbon electrode by means of cyclic (CV) and square-wave voltammetry (SWV). We also studied voltametrically the interactions between capsaicin and some vitamins present in pepper extracts. Redox features of vitamin E, ascorbic acid, and quercetin have been taken for consideration in voltammetric experiments of capsaicin with CV and SWV. From the features of the voltammograms we could observe indications of interactions between capsaicin and co-extracted vitamins and quercetin. We proposed a simple voltammetric methodology for estimation of the antioxidative potential of these compounds. By using the features of the voltammetric responses of equimolar mixture containing all four compounds (capsaicin, vitamin E, quercetin and ascorbic acid) as a referent system, we could estimate the antioxidative potential of the hot peppers extracts

Development and validation of reverse phase high performance liquid chromatographic method for determination of Tirofiban in serum

А specific, sensitive and rapid RP-HPLC method has been developed for the determination of Tirofiban in serum. The chromatographic separation was realized using reverse phase LiChrospher® 100 RP-18 column (4.0 mm × 250 mm, 5 μm) and mobile phase consisting the mixture of 0.1 M KH2PO4 (pH 5.2, adjusted with 1.0 N sodium hydroxide solution) and acetonitrile, with the ratio of 70:30% (v/v) and flow rate of 1.0 ml/min. The detection was carried out at 274 nm. The response was linear over the range of 0.03 – 0.18 mgmL-1 in mobile phase and serum samples. The limit of detection (LOD) for Tirofiban was 1.84, 13.8 and 14.6 μg mL-1 in methanol, spiked rat serum and spiked human serum, respectively. The described method can be quickly and routinely applied, without any interference from endogenous substances, for therapeutic monitoring of levels of Tirofiban in the serum samples

Development and validation of HPLC method for content determination of Meloxicam in injections

The principal aim of this paper is to establish and validate a rapid, simple, and economical approach that employs high-pressure liquid chromatography, capable of routinely assessing the content of Meloxicam present in injections. To accomplish this goal, it is necessary to meet the requirements outlined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, as well as the specifications delineated in the contemporary editions of the internationally recognized pharmacopeias that pertain to the design and validation of analytical methodologies. The analytical methodology was performed with the utilization of a high-performance liquid chromatography system, Waters Alliance (Waters corporation, USA), consisting of a quadrupole pump, an e-2695 separation module, and an automatic sampler. The optimization of the detection wavelength was accomplished using the Waters 2489 UV/Vis detector and Empower 3 software was employed for data processing. Separation was achieved via the deployment of a LiChrospher 100, RP-18 (5 μm) column. The mobile phase used in the study consisted of a combination of Acetonitrile and ultrapure water, in a 60:40 ratio, respectively. The pH of the water component was subsequently adjusted to 3.1 with the addition of glacial acetic acid. This reversed-phase column approach, using an isocratic method, was then utilized for the successful validation of the analytical method. According to the obtained results, the developed analytical method exhibits accuracy and precision under consistent conditions over a limited period and on a single sample, as well as precision when conducted in the same laboratory on the same day by two analysts. Furthermore, the method is specific, linear across the range, and robust against variations in the ratio of the mobile phase components, the pH of the water in the mobile phase, and the flow rate. These findings support the utility and reliability of the developed methodology for the routine determination of Meloxicam content in injections. In conclusion, the reversed-phase column approach using an isocratic method proved to be a successful and robust analytical method for the determination of Meloxicam content in injections. This fast, simple, and cost-effective alternative offers a promising solution for the analysis of other related drugs with similar chemical properties. Furthermore, the simplicity and ease of application of this method offer significant advantages, as it does not require any special preparation of the working environment or prior training of the analyst. Thus, this method represents a valuable contribution to the field of pharmaceutical analysis, and it may facilitate the quality control of Meloxicam-containing products. Overall, this study provides a foundation for further development and optimization of analytical methods for the analysis of other drugs with similar properties, leading to better quality control and improved patient safety

Развој и валидација на RP-HPLC метод за определување на 2-феноксиетанол во козметички производи

Феноксиетанолот е хемиско соединение кое широко се користи во козметиката и фармацијата. Се употребува како конзерванс во производите за нега на кожа. Во медицината, служи како стабилизатор за вакцини и како средство за дезинфекција во офталмолошки раствори. Изложеноста на феноксиетанол е поврзана со реакции кои се движат од егзема до сериозни алергиски реакции. Затоа, одредувањето на 2-феноксиетанол во козметичките и фармацевтските производи е од клучно значење за да се обезбеди нивната безбедност. Наша цел беше да развиеме едноставен RP-HPLC метод со UV детекција за одредување на конзервансот 2-феноксиетанол во комерцијално достапните козметички производи. Методот беше валидиран со определување на параметрите: соодветност на системот, специфичност, линеарност, опсег, точност, прецизност, граница на детекција и граница на квантификација. Потоа, методот беше применет за одредување на 2-феноксиетанол во 10 различни козметички производи за нега на кожа. Предложениот RP-HPLC метод овозможува едноставно, точно, прецизно и брзо одредување на 2-феноксиетанол во козметичките производи. Предностите на методот вклучуваат едноставна подготовка на примерокот, добра прецизност (RSD помала од 2%) и добар аналитички принос (поголем од 99%). Границата на детекција (LOD) и границата на квантификација (LOQ) беа 0,0243 mg/ml и 0,0738 mg/ml, соодветно