Detection of sulfur‐containing impurities in pharmaceutical samples by high performance liquid chromatography/chemical reaction interface mass spectrometry

Abstract

This paper describes the use of chemical reaction interface mass spectrometry (CRIMS) combined with liquid chromatography for the detection of trace level sulfur-containing impurities in pharmaceutical materials. A mixture of sulfur- and non-sulfur-containing compounds were analyzed initially to test the system. Then the determination of trace level impurities in a cimetidine drug substance was carried out. Detection of sulfur-containing impurities at less than 0.1% of the major component was obtained with good linearity. The results obtained are consistent with the expected results for this sample and illustrate the applicability of the technique.

Chemical Reaction Interface Mass Spectrometry with High Efficiency Nebulization

“…Reaction products of interest (CO 2 in this study) are analyzed by a quadrupole MS (model 5971 HP MSD, Agilent Technologies, Foster City, CA) equipped with an electron impact ion source connected to the chemical reaction interface through a heated fused-silica capillary (320-µm i.d.). The operating conditions are optimized for the best signal-to-noise ratio for m/z 44 (CO 2 + ) by adjusting the SO 2 flow (∼2 × 10 6 counts/s for 32 S 16 O 2 + signal).…”

“…The analytes introduced into the MIP cavity react with the reactant gas, and the stable products are detected by a mass spectrometer after electron impact ionization. This approach is in fact a generalization to IRMS, offering a variety of reactions suitable for detection of different elements. − Note that IRMS is limited to combustion by oxygen.…”

“…This approach is in fact a generalization to IRMS, offering a variety of reactions suitable for detection of different elements. [14][15][16] Note that IRMS is limited to combustion by oxygen. Liquid sample introduction in CRIMS requires an interface that produces small analyte particles devoid of solvent and entrained by a carrier gas free from solvent vapor.…”

Sulfur-Specific Detection of Impurities in Cimetidine Drug Substance Using Liquid Chromatography Coupled to High Resolution Inductively Coupled Plasma Mass Spectrometry and Electrospray Mass Spectrometry

“…In the pharmaceutical industry, the detection and identification of impurities/metabolites structurally related to the drug substance are of utmost importance. Conventional methods of analysis to detect, track, quantify, and identify drug substances and related impurities use molecular mass spectrometry via atmospheric pressure ionization (API-MS) , or, in the case of drug metabolism and pharmacokinetics, use radiolabeling. ,, A significant number of drug substances contain heteroatoms that can be detected using element-specific detectors such as inductively coupled plasma mass spectrometry (ICP-MS) or chemical reaction interface mass spectrometry (CRIMS) . Structurally related compounds can then be more easily identified.…”