A new derivatization reagent for LC–MS/MS screening of potential genotoxic alkylation compounds

Wijk, A. M. van; Niederländer, H.A.G.; Siebum, Arjan H. G.; Vervaart, M.A.T.; Jong, G.J. de

doi:10.1016/j.jpba.2012.10.004

Cited by 20 publications

(17 citation statements)

References 17 publications

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“…Fig. 6 shows the separation of the BPPC derivatives G, K, T and M using the CE-MS method as well as the earlier reported LC-MS method [9], demonstrating the complementary separation characteristics of these methods. For the test components, a reverse elution order is shown for the mass-tocharge based CE separation compared to HILIC separation.…”

Section: Selectivity Of Separationmentioning

confidence: 55%

“…Formic acid, ammonium formate, phosphoric acid, TRIS, HPLC grade water and acetonitrile were obtained from Baker (Deventer, Netherlands). The reagent butyl 1-(pyridinyl-4yl) piperidine 4-carboxylate (BPPC), was synthesized in house [9]. In order to investigate detectability of the derivatization products different type of API were used to simulate realistic conditions.…”

Section: Chemicalsmentioning

confidence: 99%

“…The method is based on selective derivatization of alkyl halides and mesylate esters with reagents 4-dimethylaminopyridine (DMAP) or butyl 1-(pyridinyl-4yl) piperidine 4-carboxylate (BPPC), liquid chromatography (LC) separation and tandem-mass spectrometry (MS-MS) detection of reagent related fragments [8,9]. The detection of a neutral loss, related to the loss of the reagent from the derivative, indicates the presence of a PGI.…”

Section: Introductionmentioning

confidence: 99%

“…To prevent major ionization suppression, it is desirable to separate the derivatives from the API, the excess of reagent and other matrix constituents. Hydrophilic interaction chromatography (HILIC) has been shown to be suitable for the purpose [6,8,9]. However, one or more complementary methods may be required to achieve a sufficiently high level of coverage for unknown potential genotoxic impurities.…”

Section: Introductionmentioning

confidence: 99%

“…In addition the effect of applying either of the two different derivatization reagents on separation has been investigated. Although presented as a method for target analysis in full scan MS mode, when used in combination with triple quadrupole tandem-MS the method can also be applied as an untargeted screening method for alkylating components, i.e., based on reagent based neutral loss detection [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Sensitive CE–MS analysis of potentially genotoxic alkylation compounds using derivatization and electrokinetic injection

Wijk

Niederländer²,

Ogten

et al. 2015

Analytica Chimica Acta

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Section: Selectivity Of Separationmentioning

confidence: 55%

Section: Chemicalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sensitive CE–MS analysis of potentially genotoxic alkylation compounds using derivatization and electrokinetic injection

Wijk

Niederländer²,

Ogten

et al. 2015

Analytica Chimica Acta

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Capillary electrophoretic methods for quality control analyses of pharmaceuticals: A review

Řemínek

Foret

2020

Electrophoresis

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Capillary electrophoresis represents a promising technique in the field of pharmaceutical analysis. The presented review provides a summary of capillary electrophoretic methods suitable for routine quality control analyses of small molecule drugs published since 2015. In total, more than 80 discussed methods are sorted into three main sections according to the applied electroseparation modes (capillary zone electrophoresis, electrokinetic chromatography, and micellar, microemulsion, and liposome-electrokinetic chromatography) and further subsections according to the applied detection techniques (UV, capacitively coupled contactless conductivity detection, and mass spectrometry). Key parameters of the procedures are summarized in four concise tables. The presented applications cover analyses of active pharmaceutical ingredients and their related substances such as degradation products or enantiomeric impurities. The contribution of reported results to the current knowledge of separation science and general aspects of the practical applications of capillary electrophoretic methods are also discussed.

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Determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid by derivatization followed by high‐performance liquid chromatography with ultraviolet detection

Zhou

Liu

et al. 2017

J of Separation Science

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Methanesulfonic acid is routinely used in pharmaceuticals but can contain potentially genotoxic impurities such as methyl methanesulfonate and ethyl methanesulfonate. The aim of this study was to develop a simple high-performance liquid chromatography with ultraviolet detection method for determining methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid. Samples (250 mg) in water/acetonitrile (200 μL) were first combined with 10.0 mol/L sodium hydroxide solution (270 μL). Then they were mixed with 2.0 mg/mL N,N-diethyldithiocarbamate (500 μL), diluted to 5 mL with N,N-dimethylacetamide and allowed to react at 80°C for 1 h. The derivatives were analyzed using gradient high-performance liquid chromatography with ultraviolet detection (277 nm) and structurally elucidated by liquid chromatography with mass spectrometry. With acetonitrile/5 mmol/L ammonium acetate solution as the eluent and 1 mL/min as the flow rate on a C18 column, the derivatives were eluted at 10.6 and 14.8 min. Good linearity (correlation coefficients > 0.999) and low limits of quantitation (0.6 ppm) were obtained. The recoveries were in the range of 80-115% with relative standard deviation < 5.0%. Finally, the established method was successfully used for the determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid.

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A new derivatization reagent for LC–MS/MS screening of potential genotoxic alkylation compounds

Cited by 20 publications

References 17 publications

Sensitive CE–MS analysis of potentially genotoxic alkylation compounds using derivatization and electrokinetic injection

Sensitive CE–MS analysis of potentially genotoxic alkylation compounds using derivatization and electrokinetic injection

Capillary electrophoretic methods for quality control analyses of pharmaceuticals: A review

Determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid by derivatization followed by high‐performance liquid chromatography with ultraviolet detection

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