Category Archives: AMM 2019, Volume 65, Number 2

The Statistical Analysis of Pharmacokinetic Parameters in the Context of Bioequivalence Testing of Two Anthelmintic Formulas Based on Ivermectine and Triclabendazole in Sheep

Lenard Farczadi1, Laurian Vlase2, Orsolya Melles3, Ramona Tolomeiu4, Octavia Tamas-Krumpe4, Andreea Buta4, Laurentiu Ognean4

1. University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania
2. “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
3. Clinical and Analytical Research Center Vim Spectrum
4. University of Agricultural Science and Veterinary Medicine Cluj-Napoca, Romania

DOI: 10.2478/amma-2019-0015

Conducting bioequivalence studies is an essential step during the market authorization process of generic pharmaceutical formulations, for both human or veterinary use. The aim of the present study was to evaluate the pharmacokinetics of triclabendazole sulphoxide, the main metabolite of triclabendazole, and ivermectin in order to evaluate the bioavailability and bioequivalence of a novel sheep anthelmintic formulation of oral suspension for sheep treatment containing triclabendazole 50 mg/mL and ivermectin 1 mg/mL compared to the reference product. In order to determine relative bioavailability of the test product with respect to the reference product the study was conducted on 36 clinically healthy sheep, following an unicentric, randomized, cross-over, two-sequence, two-treatment and 14-day wash-out study design. For the determination of triclabendazole sulphoxide and ivermectin sheep plasma concentrations, two rapid, selective high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) methods were developed and validated. The measured plasma concentrations of triclabendazole sulphoxide and ivermectin were used for the pharmacokinetic analysis and the determination of bioequivalence between the test product with regards to the reference product. The noncompartmental analysis of the pharmacokinetic data for both triclabendazole sulphoxide and ivermectin showed similarities between first-order kinetics of the test and reference product. The relevant pharmacokinetic parameters (Cmax, AUClast, AUCtot) were determined and the bioequivalence between the test and reference product could be concluded.

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Development and Validation of an UV-Spectrophotometric Method for the Assay of Strontium Ranelate and HPLC Stability Testing from Bulk and Pharmaceutical Dosage Form

Béla Kovács1, Réka Molnár2, Előd Ernő Nagy3, Éva Katalin Kelemen4, Blanka Székely-Szentmiklósi3, István Székely-Szentmiklósi4,5, Boglárka Kovács-Deák6, Árpád Gyéresi7

1. University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Romania
2. First Department of Internal Medicine, Faculty of Medicine, University of Szeged, Hungary
3. Department of Biochemistry and Environmental Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Romania
4. Gedeon Richter, Târgu Mureș, Romania
5. Department of Pharmaceutical Industry and Management, Faculty of Pharmacy, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Romania
6. Salvator Pharmacy, Târgu Mureș, Romania
7. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Romania

DOI: 10.2478/amma-2019-0014

Objective: The present work offers a fast, reliable and easy UV spectrophotometric method for the assay of strontium ranelate from bulk samples and pharmaceutical dosage form.
Methods: The proposed method uses 0.1% V/V trichloroacetic acid as dissolution medium for spectrophotometric analysis, by signal detection at 321 nm. The method was validated according to the currently in-force international guidelines for linearity, accuracy, precision, robustness, limit of detection and quantification.
Results: The method was found to be linear in the range of 5-100 µg mL-1 (R2 > 0.999). Method accuracy was found in-between 98.87-100.41%, showing good linear correlation as well (R2 = 0.9997). The concentrations for limit of detection and limit of quantitation were found 1.13 µg mL-1 and 3.77 µg mL-1, resp. The proposed method showed good intra- and interday precision, with low RSD values of 0.53-1.24% and 1.11%, resp.
Conclusions: Stability studies performed by both HPLC and UV spectrophotometric methods revealed that the active substance is highly susceptible to acidic hydrolysis, oxidation and exposure to high temperature.

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Analytical Quality by Design with the Lifecycle Approach: A Modern Epitome for Analytical Method Development

Maher Abdulrazzaq Alhakeem1, Mihaela Violeta Ghica2, Cristina Dinu Pîrvu2, Valentina Anuța2, Lăcrămioara Popa2

1. University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
2. Department of Physical and Colloidal Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania

DOI: 10.2478/amma-2019-0010

Quality by Design is the methodical method to development concept that starts with the predefined objects. The method put emphasis on the process of development of a product, the control process, which is built on risk management and comprehensive knowledge of science. The concept of QbD applied to analytical method development is known now as AQbD (Analytical Quality by Design). Comprehension of the Analytical Target Profile (ATP) and the risk assessment for the variables that can have an impact on the productivity of the developed analytical method can be the main principles of the AQbD. Inside the method operable design region (MODR), the AQbD permits the movements of the analytical methods. This paper has been produced to discuss various views of analytical scientists, the comparison with conventional methods, and the phases of the analytical techniques.

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Development and Validation of an UHPLC Method for Ostarine Determination in Dietary Supplements

Amalia Miklos1, Amelia Tero-Vescan1, Lénárd Farczádi2,3, Daniela-Lucia Muntean1

1. Faculty of Pharmacy, University of Medicine, Pharmacy, Sciences and Technology of Tîrgu Mureș, Tîrgu Mureş, Romania
2. Center for Advanced Medical and Pharmaceutical Research (CCAMF), University of Medicine, Pharmacy, Sciences and Technology of Tîrgu Mureș, Tîrgu Mureş, Romania
3. Faculty of Pharmacy, University of Medicine and Pharmacy „Iuliu Hațieganu” Cluj-Napoca, Cluj-Napoca, Romania

DOI: 10.2478/amma-2019-0008

Objective: The purpose of this study was to develop a low-cost, yet sensitive and precise UHPLC method for the quantitative determination of ostarine from dietary supplements (DS) for athletes. The analytical performance of the method was verified on a DS legally acquired from a specialized website for athletes. The uniformity of mass and content of the ostarine DS was also verified.
Methods: For the quantitative determination of ostarine a UHPLC method was developed and validated. The separation was performed using a reversed-phase C18 column, using a mixture of 75% methanol: 25% formic acid 0.1% in isocratic elution, at a flow rate of 0.5 ml/min. The uniformity of mass and content of DS was performed following the methodology described in the European Pharmacopoeia 7th Edition.
Results: The validated method was specific and linear on the concentration range of 1-25 µg/ml and was precise and accurate at all concentration levels, according to the official guidelines for validating analytical methods. An average mass of 510 mg content was obtained for the ostarine capsules, with an RSD of 2.41%. Regarding the uniformity of the content, an average of 4.65 mg ostarine/capsule was obtained with an RSD of 1.05%.
Conclusions: The developed UHPLC method was suitable, rapid, sensitive and allowed quantitative determination of active substance content in a DS with ostarine (92.91% ostarine/capsule from 5 mg ostarine/capsule declared by the manufacturer).

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New UHPLC Method for Cannabidiol Determination in Hard Capsules

Robert-Alexandru Vlad, Lenard Farczadi, Silvia Imre, Adriana Daniela Ciurba, Nicoleta Todoran, Emoke Redai, Paula Antonoaea, Daniela Lucia Muntean

University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Romania

DOI: 10.2478/amma-2019-0007

Objectives: The aim of the study was to propose a new UHPLC method for the determination of cannabidiol (CBD) from supplements and drugs available on the Romanian market. Materials and methods: The HPLC assay of CBD was achieved by using a Phenomenex Gemini NX-C18 column. The mobile phase consisted of 70% acetonitrile and 30% water. Elution was performed in isocratic mode and the detection was done at 208 nm. The method was tested on hard capsules containing 150 mg of CBD.
Results and discussions: The retention time of CBD was 2.8 minutes. Regression analysis showed good linearity over the 1-100 ug/ml concentration range. The lowest limit of quantification was established at 1 µg/ml. The method was developed by using reconstituted capsules. The substance proved low stability in solution at room temperature and stability at temperatures between 2-8ºC. The recovery of reconstituted samples was 96.77%. The commercial capsules had a very low content of 15-20% from declared content.
Conclusions: The proposed method can be used for CBD determination in different pharmaceutical formulations – hard and soft capsules with coconut oil as excipient.

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Dental Students’ Tobacco Smoking Habits, Second-hand Smoke Exposure, and Training in Cessation Counselling at the University of Medicine Pharmacy Sciences and Technology of Târgu Mureș

Márta Germán-Salló1, Zoltan Preg1, Dalma Bálint Szentendrey1, Enikő Nemes-Nagy1, Mihály Imre László1, Zita Fazakas1, Edith Simona Ianosi1, Pál István Kikeli2, Zoltán Ábrám1, Péter Balázs3

1. University of Medicine Pharmacy Sciences and Technology of Targu Mures, Romania
2. Procardia Medical Unit, Targu Mures, Romania
3. Semmelweis University, Budapest, Hungary

DOI: 10.2478/amma-2019-0006

Objectives: To describe tobacco smoking habits, attitudes, second-hand smoke exposure, and training in cessation counseling at the University of Medicine Pharmacy, Sciences and Technology of Târgu-Mureș (UMPSTTM), as baseline data for the first Romanian university to implement a Smoke-Free University Project.
Methods: A cross-sectional survey was administered in 2014 among dental students at UMPSTTM to explore their smoking habits, attitudes toward smoking and tobacco control policies, exposure to second-hand smoke, interest in quitting, and their knowledge about cessation counseling. We used core questions of the Global Health Professions Student Survey (GHPSS) and added specific items related to the Smoke-Free University Project. Data were analyzed by SPSS v22 software. We compared our results with those of the GHPSS Survey.
Results: 581 dental students, 73.1% of the target population (n=795), completed the questionnaire. 38.7% were current smokers. Approximately 1 in 5 (22.6%) current smokers admitted smoking inside university buildings, although 80.7% were aware of the smoking ban. 44.2% of current smokers plan to quit smoking. Nearly half of the students (48.9%) were exposed to second-hand smoke in their current homes, 78.1% in public places and 33.3% inside the university buildings. Only 21.0% of all participants received any formal training on how to help future patients quit.
Conclusions: Tobacco use prevalence was higher among future dentists than in the majority of respondents to the GHPSS. Changes in dental school education are needed to promote personal smoking cessation, as well as to educate dentists on how to support their future patients quitting.

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