scholarly journals N-nitrosamine Impurities in Medicines: Toxicity, Formation Pathways, Methods of Determination, and Limits (Review)

2020 ◽  
Vol 9 (4) ◽  
pp. 180-190
Author(s):  
P. P. Shchetinin ◽  
S. P. Senchenko ◽  
K. K. Gordeev
Keyword(s):  
High Performance ◽  
Pharmaceutical Products ◽  
Gas Chromatography Mass Spectrometry ◽  
Medicinal Products ◽  
Angiotensin Ii Receptor ◽  
Pharmaceutical Ingredients ◽  
Current State ◽  
Golden Standard ◽  
Receptor Blockers ◽  
And Control

Introduction. N-nitrosamine compounds are potent genotoxic agents in animal species and some are classified as probable human carcinogens. This group of genotoxic impurities was found in drugs such as angiotensin II receptor blockers, histamine H1 receptor antagonists, and synthetic antidiabetic drugs. This discovery caused a flurry of alarm in the global pharmaceutical industry and resulted in a series of international investigations trying to determine root causes of nitrosamine formation in medicinal products and to find ways to minimize risks associated with nitrosamine contamination.Text. This paper provides an overview of the current state of the problem. It summarises the main pathways of N-nitrosamine formation in medicinal products at the stages from synthesis of active pharmaceutical ingredients to storage of finished pharmaceutical products. The paper describes the main mechanism responsible for the toxic effect of this group of impurities in human body. It also describes methods of extraction and analysis of N-nitrosamines found in medicinal products. It was demonstrated that high-performance liquid chromatography and gas chromatography-mass spectrometry are a golden standard for the detection of these contaminants. The paper also touches upon the main principles of setting limits for nitrosamine impurities in medicinal products.Conclusion. The data presented give a picture of the root causes of N-nitrosamine formation in medicinal products, as well as current detection and control methods used worldwide. Meanwhile, the paper raises a key issue about the need to develop Russian standards that would control the purity of medicinal products in terms of N-nitrosamine impurities. For that end, it will be necessary to draw on the experience of the leading USA and EU regulatory authorities.

scholarly journals Nitrosamine Impurities: Origin, Control and Regulatory Recommendations

2021 ◽  
Vol 9 (2) ◽  
pp. 77-80
Author(s):  
Umesh Dobariya ◽  
Narendra Chauhan ◽  
Himani Patel ◽  
Nidhi Pardeshi
Keyword(s):  
Risk Assessment ◽  
Pharmaceutical Product ◽  
Regulatory Agencies ◽  
Unexpected Finding ◽  
Angiotensin Ii Receptor ◽  
Drug Products ◽  
Human Carcinogen ◽  
Receptor Blockers ◽  
Risk Assessment Strategy ◽  
And Control

The unexpected finding of presence of nitrosamine impurities, by USFDA and EMA in year 2018, in drugs such as Angiotensin-II Receptor Blockers (ARBs), Ranitidine, Nizatidine and Metformin, has triggered the need for a risk assessment strategy for evaluation and control of these probable human carcinogen - nitrosamine in pharmaceutical product that are at risk. This finding leads to voluntarily recall of products worldwide. The finding of nitrosamines in some types of drug products led FDA and other international regulators to conduct a detailed risk assessment of these impurities in APIs and drug products. Although nitrosamine impurities have been found in only some drug products, regulatory agencies recommended to extend risk analysis in other chemically synthesized APIs and drug products also.

scholarly journals Determining Undeclared Synthetic Pharmaceuticals as Adulterants in Weight Loss Herbal Medicines

2020 ◽  
Vol 10 (1) ◽  
pp. 26253
Author(s):  
Babak Salahshour ◽  
Sajjad Sadeghi ◽  
Hajar Nazari ◽  
Kambiz Soltaninejad
Keyword(s):  
Weight Loss ◽  
High Performance ◽  
Herbal Medicines ◽  
Drug Market ◽  
Gas Chromatography Mass Spectrometry ◽  
Array Detector ◽  
Active Pharmaceutical Ingredients ◽  
Diode Array Detector ◽  
Pharmaceutical Ingredients ◽  
Health Authorities

Background: The popularity and use of herbal medicines and supplements are growing worldwide. Herbal anti-obesity products have been considered as suitable alternatives to synthetic pharmaceuticals as they are introduced as harmless natural products. However, some manufacturers often add undeclared synthetic pharmaceuticals to the anti-obesity herbal medicine products to improve their efficacy and potency. The present study aimed to analyze herbal weight loss products collected from the drug market in Bojnurd City, Iran.Methods: Ninety-six herbal drug samples, as weight loss products, were obtained from herb shops and pharmacies in Bojnurd City, Iran. All samples were analyzed to detect undeclared active pharmaceutical ingredients using High-Performance Liquid Chromatography with Diode Array Detector (HPLC-DAD) and Gas Chromatography-Mass Spectrometry (GC-MS) techniques.Results: Caffeine, trimethoxyamphetamine, and vitamin E were identified in herbal weight loss products. Caffeine was detected in 21.8% of the obtained samples, as the most common undeclared active pharmaceutical adulterant. Conclusion: Undeclared active pharmaceutical ingredients in herbal weight loss products could threaten patients’ health. Thus, it is necessary to create awareness through health authorities in this regard.

scholarly journals Quantitative determination of caffeine in different matrices

2016 ◽  
Vol 62 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Nevena Grujić-Letić ◽  
Branislava Rakić ◽  
Emilia Šefer ◽  
Maja Milanović ◽  
Maja Nikšić ◽  
...  
Keyword(s):  
Surface Water ◽  
High Performance ◽  
Energy Drinks ◽  
Pharmaceutical Products ◽  
Hplc Method ◽  
Narcotic Analgesics ◽  
Human Waste ◽  
Caffeine Content ◽  
And Control

Caffeine is odorless, bitter taste substance which can be naturally found in coffee, cocoa, tea leaves, and is intentionally added in food and pharmaceutical products. It can also be found in surface water in small concentrations where is often used as an excellent indicator of human waste. The aim of the work is determination of caffeine content in food, beverages, analgesics and surface water using solidphase extraction followed by high-performance liquid chromatography (HPLC). Caffeine content was determined in 12 commercial tea and coffee products, non-alcoholic energy drinks and food, 5 combined preparations of analgesics and the Danube samples collected from 7 representative locations. The results showed that caffeine content in food ranged 5,6-158 mg/100 g, tea samples 24,71-30,81 mg/100 ml, coffee samples 1328-3594 mg/100 g, energy drinks 9,69-30,79 mg/100 ml and in the Danube samples 15,91-306,12 ng/l. Caffeine content in combined commercial formulations of non-narcotic analgesics of all brands did meet specifications. The data suggested that the proposed HPLC method can be used for routine determination and control of caffeine content in different matrices.

scholarly journals Status of Labor Productivity in Kemerovo Region

2019 ◽  
Vol 4 (2) ◽  
pp. 201-206
Author(s):  
Владислав Анискин ◽  
Vladislav Aniskin ◽  
Татьяна Бельчик ◽  
Tatyana Belchik
Keyword(s):  
Labor Productivity ◽  
High Performance ◽  
Personal Interest ◽  
Factors Affecting ◽  
Current State ◽  
Raising Awareness ◽  
Fixed Assets ◽  
The Russian Federation ◽  
Productivity Dynamics ◽  
And Control

The article considers the level and dynamics of labor productivity in the Kemerovo region in comparison with the Russian Federation. The research objective was to reveal the current state of the local labor productivity. A number of statistical problems were revealed as a result of an analysis of labor productivity dynamics and highly productive jobs. The author determines the main factors affecting the level of labor productivity and suggests measures to eliminate them. The study was based on statistical data, as well as research results of Russian and foreign analysts. The analysis involved both absolute and relative values, methods of comparison, grouping and analysis. The author believes that the low level of labor productivity in the region can only be increased by the combined efforts of the state and individual enterprises. The set of measures should include reduction of the depreciation of fixed assets, improvement of statistical reporting, raising awareness and control over labor productivity, raising the level of skills and personal interest of employees in high-performance work, and stimulating enterprises.

scholarly journals Quality of injectable oxytetracycline circulating in legal markets of Addis Ababa, Ethiopia using physiochemical and sterility analysis

2021 ◽  
Vol 25 (2) ◽  
pp. 14-26
Author(s):  
Yosef Nigussie ◽  
Achenef Melaku ◽  
Misgana Tadese ◽  
Bizuayehu Belete ◽  
Elias Kebede
Keyword(s):  
High Performance ◽  
Addis Ababa ◽  
Physicochemical Characteristics ◽  
Pharmaceutical Products ◽  
World Health ◽  
Veterinary Drug ◽  
Pharmaceutical Ingredients ◽  
Direct Inoculation ◽  
Health Organization

This study was conducted to evaluate the quality of different brands of injectable oxytetracycline solutions circulating in the legal markets  of Addis Ababa with respect to physicochemical characteristics and sterility. Nine brands of oxytetracycline with thirteen different batches were randomly purchased from veterinary drug stores in the city. The physical assessment was performed by using a checklist that was  prepared based on the World Health Organization guidelines. The qualitative and quantitative analysis of active pharmaceutical ingredients (API) was performed by High-Performance Liquid Chromatography. The sterility test was assessed by using the direct  inoculation method. All samples passed the identity, the assay, and the sterility tests. However, there were statistically significant  differences (P<0.05) among brands in the quantity of API. The highest percentage of the API was recorded in brand G (112.12%± 1.86) while the lowest was seen in brand H (92.61%± 1.5). This study revealed that all brands passed both physicochemical and sterility tests except for the differences in the API level among brands. Strict regulation, monitoring, and wider-scale surveillance are required to assure sustainable control of substandard, unsterile, and falsified pharmaceutical products in the country.

scholarly journals Paper Analytic Device to Detect the Presence of Four Chemotherapy Drugs

2018 ◽  
pp. 1-10
Author(s):  
Madeline Smith ◽  
Ayenew Ashenef ◽  
Marya Lieberman
Keyword(s):  
High Performance ◽  
Dosage Forms ◽  
Patient Treatment ◽  
Internal Validation ◽  
Bar Code ◽  
Chemotherapy Drugs ◽  
Color Changes ◽  
Pharmaceutical Ingredients ◽  
Wax Printing ◽  
And Control

A paper analytic device, the chemoPAD, was developed and validated to visually detect methotrexate, doxorubicin, cisplatin, and oxaliplatin at concentrations commonly found in injectable dosage forms. By testing residual solution after patient treatment, the chemoPAD can be used to monitor drug quality without restriction of patient access to medication. The chemoPAD is produced by wax printing on Ahlstrom paper to create separate reaction areas and deposits small amounts of chemicals to create color changes in response to different active pharmaceutical ingredients (APIs). This creates a unique color bar code to identify each medication. Internal validation studies show that the chemoPAD has excellent sensitivity and specificity to differentiate between samples of 100% and 0% API, which is the distinction relevant to the majority of reported falsified chemotherapy cases. The platinum-containing drugs, cisplatin and oxaliplatin, can be detected semiquantitatively. The cards can be read either visually by comparison with a standard image or by using computer image analysis. Dosage forms were collected from the Ethiopian health care system and analyzed with the chemoPAD followed by high-performance liquid chromatography. A substandard sample was discovered and reported to the Ethiopian Food Medicine and Healthcare Administration and Control Authority.

The Impact of Angiotensin-II Receptor Blockers on Cardiovascular Events in Hypertensive Patients – Evidence from Real-life Databases

2010 ◽  
Vol 6 (3) ◽  
pp. 33
Author(s):  
Robert J Petrella ◽  
Keyword(s):  
Angiotensin Ii ◽  
Antihypertensive Drugs ◽  
Real Life ◽  
Angiotensin Ii Receptor Blockers ◽  
Angiotensin Ii Receptor ◽  
Real World Setting ◽  
Actual Experience ◽  
Receptor Blockers ◽  
Randomised Controlled ◽  
The Impact

It is widely recognised that hypertension is a major risk factor for the development of future cardiovascular (CV) events, which in turn are a major cause of morbidity and mortality. Blood pressure (BP) control with antihypertensive drugs has been shown to reduce the risk of CV events. Angiotensin-II receptor blockers (ARBs) are one such class of antihypertensive drugs and randomised controlled trials (RCTs) have shown ARB-based therapies to have effective BP-lowering properties. However, data obtained under these tightly controlled settings do not necessarily reflect actual experience in clinical practice. Real-life databases may offer alternative information that reflects an uncontrolled real-world setting and complements and expands on the findings of clinical trials. Recent analyses of practice-based real-life databases have shown ARB-based therapies to be associated with better persistence and adherence rates and with superior BP control than non-ARB-based therapies. Analyses of real-life databases also suggest that ARB-based therapies may be associated with a lower risk of CV events than other antihypertensive-drug-based therapies.

A Review of Angiotensin Receptor Blocker-based Therapies at all Levels of Cardiovascular Risk

2011 ◽  
Vol 7 (4) ◽  
pp. 254 ◽  
Author(s):  
Giuliano Tocci ◽  
Lorenzo Castello ◽  
Massimo Volpe ◽  
◽  
◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Hypertrophy ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Clinical Settings ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Receptor Blockers ◽  
Artery Disease

The renin–angiotensin system (RAS) has a key role in the maintenance of cardiovascular homeostasis, and water and electrolyte metabolism in healthy subjects, as well as in several diseases including hypertension, left ventricular hypertrophy and dysfunction, coronary artery disease, renal disease and congestive heart failure. These conditions are all characterised by abnormal production and activity of angiotensin II, which represents the final effector of the RAS. Over the last few decades, accumulating evidence has demonstrated that antihypertensive therapy based on angiotensin II receptor blockers (ARBs) has a major role in the selective antagonism of the main pathological activities of angiotensin II. Significant efforts have been made to demonstrate that blocking the angiotensin II receptor type 1 (AT1) subtype receptors through ARB-based therapy results in proven benefits in different clinical settings. In this review, we discuss the main benefits of antihypertensive strategies based on ARBs in terms of their efficacy, safety and tolerability.

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