Capillary electrophoresis methods for impurity profiling of drugs:A review of the past decade

Capillary electrophoresis(CE)is widely used for the impurity profiling of drugs that contain stereochemical centers in their structures,analysis of biomolecules,and characterization of biopharmaceuticals.Currently,CE is the method of choice for the analysis of foodstuffs and the determination of adulterants.This article discusses the general theory and instrumentation of CE as well as the classification of various CE techniques.It also presents an overview of research on the applications of different CE techniques in the impurity profiling of drugs in the past decade.The review briefly presents a comparison between CE and liquid chromatography methods and highlights the strengths of CE using drug compounds as examples.This review will help scientists,fellow researchers,and students to understand the applications of CE techniques in the impurity profiling of drugs.

Study on Radial Position of Impurity Ions in Core and Edge Plasma of LHD Using Space-Resolved EUV Spectrometer

Radial profiles of impurity ions of carbon, neon and iron were measured for high- temperature plasmas in large helical device （LHD） using a space-resolved extreme ultraviolet （EUV） spectrometer in the wavelength range of 60A to 400 A. The radial positions of the impurity ions obtained are compared with the local ionization energies, El of these impurity ions and the electron temperatures T,z there. The impurity ions with 0.3 keV 〈_ Ei ≤ 1.0 keV are always located in outer region of plasma, i.e., 0.7 ≤ p ≤ 1.0, and those with Ei ≤ 0.3 keV are located in the ergodic layer, i.e., 1.0 ≤ p≤ 1.1, with a sharp peak edge, where p is the normalized radial position. It is newly found that Tez is approximately equal to Ei for the impurity ions with Ei ≤ 0.3 keV, whereas roughly half the value of El for the impurity ions with 0.3 keV≤ Ei ≤ 1.0 keV. It is known that Tez is considerably lower than Ei in the plasma edge and approaches to Ei in the plasma core. Therefore, this result seems to originate from the difference in the transverse transport between the plasma edge at p 〈1.0 and the ergodic layer at p ≥ 1.0. The transverse transport is studied with an impurity transport simulation code. The result revealed that the difference appearing in the impurity radial positions can be qualitatively explained by the different values of diffusion coefficient, e.g., D=0.2 m2/s and 1.0 m2/s, which can be taken as a typical index of the transverse transport.

Influence of impurity seeding on the plasma radiation in the EAST tokamak

Plasma radiation characteristics in EAST argon（Ar） gas and neon（Ne） gas seeding experiments are studied.The radiation profiles reconstructed from the fast bolometer measurement data by tomography method are compared with the ones got from the simulation program based on corona model.And the simulation results coincide roughly with the experimental data.For Ar seeding discharges,the substantial enhanced radiations can be generally observed in the edge areas at normalized radius ρ_（pol）~0.7–0.9,while the enhanced regions are more outer for Ne seeding discharges.The influence of seeded Ar gas on the core radiation is related to the injected position.In discharges with LSN divertor configuration,the Ar ions can permeate into the core region more easily when being injected from the opposite upper divertor ports.In USN divertor configuration,the W impurity sputtered from the upper divertor target plates are observed to be an important contributor to the increase of the core radiation no matter impurity seeding from any ports.The maximum radiated power fractions f_（rad）（P_（rad）/P_（heat）） about 60%–70% have been achieved in the recent EAST experimental campaign in 2015–2016.

Implementation of a single quad MS detector in routine QC analysis of peptide drugs

A newly developed single quad mass spectrometry （MS） detector was coupled to a ultra-high perfor- mance liquid chromatography （UPLC） system and implemented in the routine quality control （QC） and impurity analysis of four therapeutic peptides, namely bleomycin sulfate, tyrothricin, vancomycin HCl and bacitracin, which were selected given their multi-component drug nature and their closely struc- turally related impurity profiles. The QC and impurity profiling results obtained using the ultra-high performance liquid chromatography ultraviolet/mass spectrometry （UPLC-UV/MS） detection system were analyzed against the results obtained using traditional high performance liquid chromatography- ultraviolet detection （HPLC-UV） methods derived from pharmacopoeial methods. In general, the used stationary phases of sub-2 μm particle （UPLC） technology resulted in lower limits of detection and higher resolution separations, which resulted in more detected impurities and shorter overall run times con- trasting the traditional HPLC columns. Moreover, online coupling with a single quad MS detector allowed direct peak identification of the main compounds as well as small impurities, hereby increasing the information content without the need of reference standards.

Quality evaluation of synthetic quorum sensing peptides used in R&D

Peptides are becoming an important class of molecules in the pharmaceutical field. Closely related peptide-impurities in peptides are inherent to the synthesis approach and have demonstrated to potentially mask biomedical experimental results. Quorum sensing peptides are attracting high interest in R＆D and therefore a representative set of quorum sensing peptides, with a requested purity of at least 95.0%, was evaluated for their purity and nature of related impurities. In-house quality control （QC） revealed a large discrepancy between the purity levels as stated on the supplier＇s certificate of analysis and our QC results. By using our QC analysis flowchart, we demonstrated that only 44.0% of the peptides met the required purity. The main compound of one sample was even found to have a different structure compared to the desired peptide. We also found that the majority of the related impurities were lacking amino acid（s） in the desired peptide sequence. Relying on the certificates of analysis as provided by the supplier might have serious consequences for peptide research, and peptide-researchers should implement and maintain a thorough in-house QC.

Combination of reversed phase liquid chromatography and zwitterion exchange-reversed phase-hydrophilic interaction mixed-mode liquid chromatography coupled with mass spectrometry for the analysis of antibiotics and their impurities

In this study, a system involving two-dimensional, column-switching high-performance liquid chromatography （HPLC） coupled with tandem mass spectrometry （LC-MS/MS） was developed and optimized for the analysis of antibiotics and their related substances. In the first-dimensional chromatography, the analytes were separated on a zwitterion exchange-reversed phase-hydrophitic interaction （ZIC-RP-HILIC） mixed-mode column coupled with tandem mass spectrometry （LC-MS/MS）. A commonly used reversed phase LC column was employed in the second-dimensional chromatography. The mobile phase for the ZIC-RP-HILIC mixed-mode chromatography consisted of a volatile buffer that was compatible with LC-MS/MS, which enhanced the efficiency of ionization for structure elucidation. The antibiotic impurities eluted in the ion-pairing reversed phase chromatography were directly characterized by the ZIC-RP-HILIC-MS system, and the orthogonal separation of ZIC-RP-HILIC mixed-mode chromatography and reversed phase LC provided extra confidence that no impurity was missed. The efficiency of this method was demonstrated in the analysis of penicillin V potassium, oxacillin sodium, ceftriaxone sodium, and their impurities. In addition, this method is convenient for impurity profiling of antibiotics, and may be used for the analysis of other pharmaceutical ingredients.

Separation and identification of moxifloxacin impurities in drug substance by high-performance liquid chromatography coupled with ultraviolet detection and Fourier transform ion cyclotron resonance mass spectrometry

In this paper, a high-performance liquid chromatography coupled with ultraviolet detection and Fourier transform-ion cyclotron resonance mass spectrometry （HPLC-UV/FrICRMS） method was described for the investigation of impurity profile in moxifloxacin （MOX） drug substance and chemical reference substance. Ten impurities were detected by HPLC-UV, while eight impurities were identified by using the high accurate molecular mass combined with multiple-stage mass spectrometric data and fragmentation rules. In addition, to our knowledge, five impurities were founded for the first time in MOX drug substance.