The objectives of the present study were to investigate the formation and rate of hydrolysis of ethyl methanesulphonate (EMS) in BMS-214662 mesylate drug substance and parenteral formulation by a gas chromatographic/mass spectrometric (GC/MS) method. EMS levels in the drug substance ranged between 0.3 microg/g and 0.8 microg/g. The parenteral formulation contains ethanol and the reaction between residual free methane sulphonic acid and ethanol may lead to the formation of EMS. Given that EMS is a potent mutagen, it is therefore of vital importance to eliminate or reduce the risk of human exposure. Data indicate no significant increase in the levels of EMS following storage of the drug product for 18 weeks at 25 degrees C or six weeks at 60 degrees C indicating that the potential reaction between ethanol and free methane sulphonic acid may not occur in the BMS-214662 formulation under the storage conditions evaluated and therefore causes no plausible safety concerns of EMS exposure in humans. Kinetic studies were conducted by spiking 200 ppb of EMS into water and the diluted and undiluted parenteral formulation. The rates of hydrolysis of EMS at 25 degrees C followed pseudo-first order kinetics and were determined to be 2.35 x 10(-4)min(-1), 67.4 x 10(-4)min(-1), and 1.32 x 10(-4)min(-1) in water, undiluted, and diluted drug product, respectively.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3109/10837450902980262 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition used in the neonatal intensive care unit.
Eur J Hosp Pharm
January 2025
Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, Utrecht, The Netherlands.
Objectives: Critically ill newborn infants often require simultaneous administration of multiple intravenous (IV) solutions through the same catheter lumen, making compatibility of these solutions crucial in neonatal intensive care units (NICUs). This study aimed to investigate the physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition (PN).
Methods: The study was conducted at the hospital pharmacy's drug compounding facility of the University Medical Centre Utrecht.
Nanosuspension Innovations: Expanding Horizons in Drug Delivery Techniques.
Pharmaceutics
January 2025
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Nanosuspensions (NS), with their submicron particle sizes and unique physicochemical properties, provide a versatile solution for enhancing the administration of medications that are not highly soluble in water or lipids. This review highlights recent advancements, future prospects, and challenges in NS-based drug delivery, particularly for oral, ocular, transdermal, pulmonary, and parenteral routes. The conversion of oral NS into powders, pellets, granules, tablets, and capsules, and their incorporation into film dosage forms to address stability concerns is thoroughly reviewed.
View Article and Find Full Text PDFDevelopment of an Adaptable Qualification Test Set for Personnel Involved in Visual Inspection Procedures of Parenteral Drug Products Manufactured Under Good Manufacturing Practice Conditions in Hospital Pharmacy Compounding Facilities.
Pharmaceutics
January 2025
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
Parenteral drug products manufactured under GMP conditions should be visually inspected for defects and particulate contamination by trained and qualified personnel. Although personnel qualification is required, no practical protocols or formal guidelines are available for the development of qualification test sets (QTSs) used for qualification procedures. The current practice is to either procure a standardized QTS from a commercial supplier or amass sufficient manufacturing rejects during visual inspection procedures to compile in-house QTSs.
View Article and Find Full Text PDFCyclodextrins and their applications in pharmaceutical and related fields.
Profiles Drug Subst Excip Relat Methodol
January 2025
Department of Pharmaceutics, Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan.
This chapter presents an overall account of cyclodextrins (CDs) with a brief description of the history, classification, and properties of these macromolecules. CDs act as complexing agents for drugs to form CD-drug inclusion complexes by various techniques. These complexes lead to the modification of the physicochemical properties of drugs to make them more soluble, chemically, and photochemically stable, and less toxic.
View Article and Find Full Text PDFPEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis.
Pharmacol Res
January 2025
Department of Cardiovascular Sciences, University of Birmingham, Birmingham, B15 2TT, UK. Electronic address:
PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here, we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity in vivo.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!