Identification and Qualification of Genotoxic Impurities as Leachables in Drug Products

2014 ◽  
pp. 466-485
Keyword(s):  
Drug Products ◽  
Genotoxic Impurities

scholarly journals A REVIEW ON ANALYTICAL CHALLENGES IN MONITORING AND CONTROLLING GENOTOXIC IMPURITIES

2020 ◽  
pp. 10-15
Author(s):  
VANDAMME S SUTNGA ◽  
RAJESH R
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Analytical Techniques ◽  
Dna Interaction ◽  
World Health ◽  
Drug Products ◽  
Genotoxic Impurities ◽  
Gas Chromatography Mass Spectroscopy ◽  
Health Organization ◽  
Analytical Approaches

Genotoxic impurities (GIs) are chemical agents that have a DNA-interaction characteristic which can ultimately lead to cancer. Their presence in various drug substances had driven various regulatory authorities to guide monitor, control, and to limit their level in various drug products. The objective of this article is to review the analytical approaches and challenges faced while accessing, monitoring, and controlling GIs in pharmaceuticals and also a brief explanation such as low limits of GIs, matrix interference, non-volatility, and environmental conditions encountered during the analysis of GIs are also discussed in this paper. At present, several modern analytical techniques are being used for the analysis of GIs such as high-performance liquid chromatography, liquid chromatography-mass spectrometry, and gas chromatography-mass spectroscopy that have high selectivity and sensitivity, but at the same time, many researchers have reported several challenges while using these techniques. Impacts of GIs are very important and various international organizations such as the World Health Organization have set out rules for regulating these chemicals. Hence, we can conclude that analytical approaches and their challenges are essential to understand because they play a key role to develop robust analytical methods.

Degradation products of proguanil — 4-chloroaniline and related components with regard to genotoxicity

2013 ◽  
Vol 67 (6) ◽  
Author(s):  
Katharina Schulz ◽  
Ulrich Oberdieck ◽  
Werner Weitschies
Keyword(s):  
Gas Chromatography ◽  
High Performance ◽  
Degradation Products ◽  
Database Analysis ◽  
Toxicological Evaluation ◽  
Drug Products ◽  
Chemical Structures ◽  
Genotoxic Impurities ◽  
Main Degradation Product ◽  
Flame Ionisation

AbstractIn the event of genotoxic impurities in drug products, knowledge of the origin and fate of these components is of particular importance. In the present study, commercially available proguanil tablets (Paludrine®) were investigated in respect of formation of the main degradation product, 4-chloroaniline (PCA), which is known to be genotoxic. The investigations made use of high performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) and gas chromatography coupled with flame ionisation detection (GC-FID) systems. In addition, proposals for the structure of further proguanil degradation products were developed based on results obtained by mass spectroscopy (HPLC-MS). Database analysis using DEREK, MCASE, and Vitic was performed to obtain an initial toxicological evaluation of the proposed chemical structures. Finally, the absence of the newly established structures in stored proguanil tablets was verified.

A Computerized Prescription Writing Program for Doctors

1985 ◽  
Vol 24 (02) ◽  
pp. 101-105
Author(s):  
C. S. Brown ◽  
S. I. Allen ◽  
D. C. Songco
Keyword(s):  
Medical Record ◽  
Drug Prescriptions ◽  
Computer Assisted ◽  
Writing Program ◽  
Typing Skill ◽  
Drug Products ◽  
Default Options ◽  
Almost All ◽  
Prescription Writing ◽  
Drug Dosages

SummaryA computer-assisted system designed to write drug prescriptions and patient instructions has been in operation in a dermatologist’s office for two years. Almost all prescriptions are generated by the machine. Drug dosages, directions, and labeling phrases are retrieved from a diagnosis-oriented formulary of 300 drug products. A prescription template with preselected default options is displayed on a terminal screen where selection is made with the use of the video pointer. Typing skill is not required, as a detailed prescription can be produced from the use of only five function keys. Prescriptions and sets of relevant instructions for the patient are computer-printed. Therapy summaries for the medical record also are automatically composed and printed.

3D Printing in Pharmaceuticals: Regulatory Perspective

2019 ◽  
Vol 24 (42) ◽  
pp. 5081-5083 ◽  
Author(s):  
Mohd. A. Mirza ◽  
Zeenat Iqbal
Keyword(s):  
New Technologies ◽  
Pharmaceutical Product ◽  
Regulatory Agencies ◽  
Major Research ◽  
Data Bases ◽  
Drug Products ◽  
Regulatory Perspective ◽  
Regulatory Guidelines ◽  
Recent Developments ◽  
Technical Issues

Background: The last few decades have witnessed enormous advancements in the field of Pharmaceutical drug, design and delivery. One of the recent developments is the advent of 3DP technology. It has earlier been successfully employed in fields like aerospace, architecture, tissue engineering, biomedical research, medical device and others, has recently forayed into the pharmaceutical industry.Commonly understood as an additive manufacturing technology, 3DP aims at delivering customized drug products and is the most acceptable form of“personalized medicine”. Methods: Data bases and search engines of regulatory agencies like USFDA and EMA have been searched thoroughly for relevant guidelines and approved products. Other portals like PubMed and Google Scholar were also ferreted for any relevant repository of publications are referred to wherever required. Results: So far only one pharmaceutical product has been approved in this category by USFDA and stringent regulatory agencies are working over the drafting of guidelines and technical issues. Major research of this category belongs to the academic domain. Conclusion: It is also implicit to such new technologies that there would be numerous challenges and doubts before these are accepted as safe and efficacious. The situation demands concerted and cautious efforts to bring in foolproof regulatory guidelines which would ultimately lead to the success of this revolutionary technology.

Quantitative Analysis of 5-Hydroxymethylfurfural in Linezolid Injection by High Performance Liquid Chromatography

2020 ◽  
Vol 16 (8) ◽  
pp. 1059-1067
Author(s):  
Jéssica Maurício Batista ◽  
Christian Fernandes
Keyword(s):  
High Performance ◽  
Potassium Phosphate ◽  
Gradient Elution ◽  
High Performance Liquid Chromatographic ◽  
Official Method ◽  
Ph Variation ◽  
Drug Products ◽  
Liquid Chromatographic Method ◽  
Liquid Chromatographic

Background: Linezolid is a synthetic broad-spectrum antibacterial belonging to the class of oxazolidinones. Linezolid for intravenous infusion is isotonized with dextrose. In acidic environment, the dehydration of dextrose produces furan derivatives, 5-hydroxymethylfurfural (5-HMF) being the main one. The determination of this degradation product is of fundamental importance, since there is evidence it is cytotoxic, genotoxic, mutagenic and carcinogenic. However, there is no official method for the determination of 5-HMF in drug products. Objective: The aim of this study was to develop and validate a high performance liquid chromatographic method to quantify 5-HMF in injection of linezolid. Methods: The chromatographic separation, after optimization, was performed on C18 (150 x 4.6 mm, 5 μm) column. Mobile phase was composed of 14 mM potassium phosphate buffer pH 3.0 ([H+] = 1.0 x 10-3) and methanol in gradient elution at 1.0 mL min-1. The injection volume was 10 μL and detection was performed at 285 nm. Results: The method was optimized and validated, showing selectivity, linearity in the range from 0.075 to 9.0 μg mL-1, precision (RSD ≤ 2.0%), accuracy (mean recovery of 100.07%) and robustness for temperature and pH variation. Conclusion: The method was shown to be adequate to determine 5-HMF in injection containing linezolid in routine analysis.

A Comprehensive Review of Regulatory Requirements and Registration Process of Pharmaceutical Drug Products in CIS Countries

2020 ◽  
Vol 7 (3) ◽  
pp. 162-176
Author(s):  
Kapil Pihwal ◽  
Neelam Pawar ◽  
Sheikh Aamir ◽  
Mohammad Shahbaz Alam ◽  
Vikas Rathee
Keyword(s):  
Regulatory Requirements ◽  
Health Value ◽  
Drug Products ◽  
Registration Process ◽  
Potential Market ◽  
Regulatory Guidelines ◽  
Cis Countries ◽  
In Cis ◽  
Regulatory Organization ◽  
Country Specific

Background: The CIS region has a potential market for India. The registration of the drug products in CIS regions is a challenging task because these countries have no harmonized regulatory organization. The CIS region includes 12 countries such as Russia, Kyrgyzstan, Ukraine, Uzbekistan, Kazakhstan, Tajikistan, Turkmenistan, Armenia, Azerbaijan, Belarus, Georgia and Moldova, which require different regulatory guidelines for medicinal product registration as per their FDA guidelines. The different guidelines for the same region become a challenging task for the manufacturer and exporter. The registration of the same product for different countries of CIS is not possible with the same dossier due to the lack of their regulatory harmonization. These countries obey their country-specific dossier format, so to target these market manufacturers and exporters needs to submit different dossier documents for different countries. But Ukraine and Kazakhstan have harmonization and it varies in Uzbekistan and Tajikistan. Ukraine and Kazakhstan are also imposing strict rules and expecting USFDA level documents for approval. Conclusion: The overall conclusion is that harmonization in CIS is highly imbalanced, which affects both time and cost for product registration. Harmonization is the need of the era for easy product registration, and it will be beneficial for the manufacturer, regulator, importer, exporter, and to access medicines of high public health value.

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