Trace level impurity method development with high-field asymmetric waveform ion mobility spectrometry: systematic study of factors affecting the performance.

For the determination of trace level impurities, analytical chemists are confronted with complex mixtures and difficult separations. New technologies such as high-field asymmetric waveform ion mobility spectrometry (FAIMS) have been developed to make their work easier; however, efficient method development and troubleshooting can be quite challenging if little prior knowledge of the factors or their settings is available. We present the results of an investigation performed in order to obtain a better understanding of the FAIMS technology.

The use of shift reagents in ion mobility-mass spectrometry: studies on the complexation of an active pharmaceutical ingredient with polyethylene glycol excipients.

Gas-phase ion mobility studies of mixtures containing polyethylene glycols (PEG) and an active pharmaceutical ingredient (API), lamivudine, have been carried out using electrospray ionization-ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry (ESI-IMS-Q-TOF). In addition to protonated and cationized PEG oligomers, a series of high molecular weight ions were observed and identified as noncovalent complexes formed between lamivudine and PEG oligomers. The noncovalent complex ions were dissociated using collision induced dissociation (CID) after separation in the ion mobility drift tube to recover the protonated lamivudine free from interfering matrix ions and with a drift time associated with the precursor complex.

Development, validation and transfer into a factory environment of a liquid chromatography tandem mass spectrometry assay for the highly neurotoxic impurity FMTP (4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine) in paroxetine active pharmaceutical ingredient (API).

This work describes the development of a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for a highly toxic impurity, FMTP (4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine), in paroxetine active pharmaceutical ingredient (API), followed by the subsequent validation of the methodology and transfer into a global production/quality control environment. The method was developed to achieve a detection limit of 10ppb mass fraction of FMTP in paroxetine API. An LC-MS/MS method was chosen because it provided the required sensitivity and selectivity with minimal sample preparation.

Investigation of the advanced functionalities of a hybrid quadrupole orthogonal acceleration time-of-flight mass spectrometer.

Time-of-flight mass spectrometry (ToF-MS) has gained wide acceptance in many fields of chemistry, proteomics, metabolomics and small molecule analysis. ToF-MS, however, has some inherent advantages and drawbacks. Numerous developments have been made to hybrid ToF instruments to improve their capabilities.

Evaluating the utility of ion mobility separation in combination with high-pressure liquid chromatography/mass spectrometry to facilitate detection of trace impurities in formulated drug products.

Many formulated products contain complex polymeric excipients such as polyethylene glycols (PEGs). Such excipients can be readily ionized by electrospray and may be present at very high concentrations, thus making it very difficult to identify trace level impurities such as degradants in samples, even if hyphenated techniques such as liquid chromatography/mass spectrometry (LC/MS) are used. Ion mobility (IM) spectrometry is a very rapid gas-phase separation technique and offers additional separation capability within the LC timeframe.

Investigation into the factors affecting accuracy of mass measurements on a time-of-flight mass spectrometer using Design of Experiment.

The results of an investigation of the parameters which have the most significant effect on the accuracy of mass measurements on a quadrupole orthogonal acceleration time-of-flight mass spectrometer (q-oaToF) are reported. The influence of eight factors is investigated: ion abundances of reference and analyte compounds, mass difference between analyte and reference compounds, quality of calibration, number of reference acquisitions averaged and TDC (time-to-digital converter) settings (resolution, Np multiplier (number of pushes correction factor), minimum number of points, i.e.

'On-the-fly' hydrogen/deuterium exchange liquid chromatography/mass spectrometry using a dual-sprayer atmospheric pressure ionisation source.

In-source 'on-the-fly' hydrogen/deuterium (H/D) exchange liquid chromatography mass spectrometry (LC/MS) has been investigated. The work was performed using a dual-sprayer source. The analyte was introduced through an electrospray ionisation sprayer and D2O was introduced through an atmospheric pressure chemical ionisation sprayer.