Identification and characterization of process related impurities in chloroquine and hydroxychloroquine by LC/IT/MS, LC/TOF/MS and NMR

A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products

“…Therefore, the actual advantage of LC-MS tools for on-line characterization of IMPs/DPs often had not been taken completely. However, the trend is changing, as evidenced in some very recent studies where the strategy similar to the one proposed by us [117] is being followed in principle [165,169,172,178,184]. Recently, some interesting features have been added in LC-MS instrumentation and controlling software like data dependent analysis (DDA), LC-MS E , mass defect filters (MDF and MMDF), 2D and 3D approaches, polarity switching, background-subtraction and noisereduction algorithms (BgS-NoRA).…”

“…In some studies, the right tool has been used, but it has not been exploited correctly. Like there has been use of TOF instrument, which was implemented only for the collection of molecular ion data and not for the fragment ions [184]. However, the use of right combination of techniques is found in some recent publications [165,169,172,175,184], which is a positive trend.…”

“…Like there has been use of TOF instrument, which was implemented only for the collection of molecular ion data and not for the fragment ions [184]. However, the use of right combination of techniques is found in some recent publications [165,169,172,175,184], which is a positive trend. (ii) Incomplete mass fragmentation pattern or incorrect structure assignment to mass fragments: Laying down fragmentation pathways for the drug and its IMPs/DPs is a very involved activity, requiring assignment of structures to multiple fragment ions.…”

Characterization of a novel impurity in bulk drug eprosartan by ESI/MSn and NMR

“…Because the impurity was generated as a byproduct when the bulk compound was synthesized, the impurity might share some common structural moieties with the synthesized target drugs [15]. Upon collision activation of the molecular ion, neutral loss of CO 2 is often observed in drugs with carbonyl acid unit [16].…”

Identification of process related trace level impurities in the actinide decorporation agent 3,4,3-LI(1,2-HOPO): Nozzle–skimmer fragmentation via ESI LC–QTOFMS

“…The use of liquid chromatography coupled with tandem mass spectrometry (MS/MS) for the characterization of impurities and degradation products has been thoroughly reviewed recently [17,19, 20], highlighting the high sensitivity and specificity of this technique. Moreover, using soft ionization MS methods, such as Electrospray (ESI) or Atmospheric Pressure Chemical Ionization (APCI), molecular mass and information about fragments can be acquired [21-24], facilitating the identification of impurities and degradation products.…”