Arylamines and aminopyridines form a class of potentially genotoxic impurities (PGIs) that can be present at trace levels in active pharmaceutical ingredients (APIs). A generic method was developed that allows the analysis of a selected set of these solutes at sub-ppm level relative to the drug substance. A highly concentrated solution of the pharmaceutical compound is analyzed by LC-MS using a single quadrupole mass spectrometer in the selected ion monitoring (SIM) mode. Since a number of target compounds show little or no retention in the reversed-phase LC setup, a fast and simple derivatization procedure using hexylchloroformate was applied. The amide derivatives of the PGI result in a higher molecular weight (more specific ion for SIM) and better chromatographic behavior. The methodology, consisting of a dual run on respectively a non-derivatized and a derivatized sample, was validated and applied to a selection of pharmaceutical substances. The method was found to be sufficiently sensitive and robust and is applicable in a QA/QC environment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.chroma.2008.08.102 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cyanomethylation of the Benzene Rings and Pyridine Rings via Direct Oxidative Cross-Dehydrogenative Coupling with Acetonitrile.
Org Lett
March 2022
College of Chemistry, Nanchang University, Nanchang 330031, PR China.
A novel and efficient approach for the amine-directed dehydrogenative C(sp)-C(sp) coupling of arylamines with acetonitrile was reported by using FeCl as the catalyst. Substituted anilines, aminopyridines, naphthylamines, and some nitrogen-containing heterocyclic arylamines react with inactive acetonitrile to form the corresponding arylacetonitriles in moderate to good yields. This protocol features nontoxic iron catalysis, efficient atom economy, nonprefunctionalized starting materials, good regioselectivity, and excellent compatibility of functional groups and aromatic rings, providing a novel, straightforward, and green approach toward arylacetonitriles.
View Article and Find Full Text PDFCo(CO) as a Solid CO (g) Source for the Amino Carbonylation of (Hetero)aryl Halides with Highly Deactivated (Hetero)arylamines.
J Org Chem
April 2021
Department of Studies in Chemistry, Manasagangotri, University of Mysore, Mysuru, Karnataka 570006, India.
Carbonylation of (hetero)aryl iodides/bromides with highly deactivated 2-aminopyridines using Pd-Co(CO) bimetallic catalysis is accomplished. The use of Co(CO) as a solid CO(g) source enhanced reaction rates observed when compared to CO(g), and excellent yields highlight the versatility of the developed protocol. A wide range of electronically and sterically demanding heterocyclic amines and (hetero)aryl iodides/bromides employed for this study resulted in excellent yields of amino carbonylated products.
View Article and Find Full Text PDFCopper-catalyzed direct amination of benzylic hydrocarbons and inactive aliphatic alkanes with arylamines.
Org Biomol Chem
May 2020
Department of Chemistry, Nanchang University, No. 999, Xuefu Rd., Nanchang, 330031, P. R. China.
A new synthetic method toward direct C-N bond formation through saturated C-H amination of benzylic hydrocarbons and inactive aliphatic alkanes with primary aromatic amines under an inexpensive catalyst/oxidant (Cu/DTBP) system has been developed. Both aminopyridines and anilines could react smoothly with primary and secondary benzylic C-H substrates or cyclohexane to form the corresponding aromatic secondary amines in moderate to good yields. This protocol has the advantages of wide functional group tolerance and use of readily available raw materials.
View Article and Find Full Text PDFIn vitro approach to elucidate the relevance of carboxylesterase 2 and N-acetyltransferase 2 to flupirtine-induced liver injury.
Biochem Pharmacol
September 2018
Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI Nano-LSI), Kanazawa University, Kanazawa, Japan.
The use of flupirtine, an analgesic, has been restricted in European countries because it causes liver injury in rare cases. Flupirtine is primarily metabolized to D-13223, an acetylamino form. In the process of D-13223 formation, it has been hypothesized that a reactive metabolite is formed which may be involved in flupirtine hepatotoxicity.
View Article and Find Full Text PDFAcetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.
Clin Ther
July 2017
Catalyst Pharmaceuticals Inc, Coral Gables, Florida, USA.
Purpose: The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes.
Methods: This was a Phase I, multicenter, open-label study of the PK properties and safety profile of amifampridine phosphate in individuals with normal, mild, moderate, or severely impaired renal function. Amifampridine phosphate was given as a single 10 mg (base equivalent) dose, and the plasma and urine PK properties of amifampridine and its 3-N-acetyl metabolite were determined.
Want 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!