Cyclic polyamide oligomers extracted from nylon 66 membrane filter disks as a source of contamination in liquid chromatography/mass spectrometry

Abstract

Background interferences are perhaps an unavoidable part of analytical detection schemes, particularly when analyzing trace level samples or when using detectors with high levels of sensitivity. In liquid chromatography, mobile phase solvents are routinely filtered using membrane filter disks to trap particulates in hopes of minimizing contamination, providing improvements in data output and instrumental operation. In this study, we report that one such filter disk leads to a significant level of contamination in LC and LC/MS experiments. Extractable compounds from nylon membrane filters generate significant background signals in UV absorption chromatograms at 214 nm, and are also detected by electrospray ionization mass spectrometry, with nominal m/z values of 453 and 679. It is shown that rinsing the nylon membranes before their use can reduce, but will not eliminate, the extractable contaminants from the mobile phase. Through MS and tandem MS analysis, we have identified these contaminants as cyclic oligomers of polyamide 66. Based on these results, it is recommended that nylon membrane filters be avoided when conducting trace level analysis, particularly when conducting LC/MS experiments. (J Am Soc Mass Spectrom 2006, 17, 652-656)

Peptide mapping of therapeutic monoclonal antibodies: Improvements for increased speed and fewer artifacts

“…Clearly, the unfiltered solvent is much cleaner than the filtered solvent. MS analysis on these ghost peaks was performed and it was determined that these peaks match common background peaks observed for Nylon 66 [30]. Therefore, it is suggested that solvents should not be filtered or be filtered only with non-nylon type filters.…”

Interferences and contaminants encountered in modern mass spectrometry

“…Interfering polydimethylcyclosiloxanes in ambient air were reported by Schlosser and Volkmer-Engert in 2003 [84] and cyclic polyamide oligomers leaching from nylon 66 filters into the LC solvent stream were described byÖnnerfjord in 2004 [85] and identified by Tran and Doucette in 2006 [86].…”

Impact of Sample Preparation on Dissolution Testing: Drug Binding and Extractable Impurities and Their Effect on Dissolution Data

“…The presence of extractables in a syringe filter introduces impurities in the sample. Not only the syringe filter but also any surface that comes in contact with the sample has the potential to introduce extractable impurities (6). The effect of extractables on downstream analysis is not always visible.…”

“…Based on absorbance measurements at 214 nm, these figures clearly show that hydrophilic PTFE membranes provided the cleanest sample for analysis because these filters did not introduce any extractable impurities into the sample. Nylon filters, on the other hand, had extractable impurities that were identified as cyclic low-molecular-weight polyamide oligomers (6). PVDF filters show intermediate behavior from the perspective of extractable impurities.…”