Determination of trace level genotoxic impurities in small molecule drug substances using conventional headspace gas chromatography with contemporary ionic liquid diluents and electron capture detection

Ho, Tien D.; Yehl, Peter; Chetwyn, Nik P.; Wang, Jin; Anderson, Jared L.; Zhong, Qiqing

doi:10.1016/j.chroma.2014.07.099

Cited by 48 publications

(26 citation statements)

References 34 publications

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“…More recently, Ho et al [26] evaluated the use of ILs as a new class of solvents for the analysis of two kinds of genotoxic impurities (alkyl/aryl halides and nitro-aromatics) in small molecule drug substances by S-HS-GC coupled to electron-capture detection (ECD). LODs (5-500 ppb of analytes in a drug substance) were up to tens of thousandsfold lower than those obtained using traditional HS-GC diluents such as DMSO.…”

Section: Applicationsmentioning

confidence: 99%

“…As commented above, the extremely low vapor pressure of ILs promoted their use as matrix media in green HS-GC-MS procedures for analysis of RSs in the pharmaceutical field [21][22][23][24][25][26]. As an example, Laus et al [21] showed the utility of using 1-N-butyl-3-methylimidazolium dimethyl phosphate ([BMIM] [DMP]) as solvent for the successful HS-GC-MS analysis of DMSO, N-methylpyrrolidone, sulfolane, tetralin, and ethylene glycol in a realistic matrix of commonly-used excipients (carboxymethylcellulose, magnesium stearate, guar flour, and corn starch) in pharmaceutical products.…”

Section: Applicationsmentioning

confidence: 99%

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Volatile sampling by headspace techniques

Soria

García-Sarrió

Sanz

2015

TrAC Trends in Analytical Chemistry

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Section: Applicationsmentioning

confidence: 99%

Section: Applicationsmentioning

confidence: 99%

Volatile sampling by headspace techniques

Soria

García-Sarrió

Sanz

2015

TrAC Trends in Analytical Chemistry

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“…The ability to control potential genotoxic impurities at low concentrations in active pharmaceutical ingredients (APIs) is vital in the development of APIs . These potential genotoxic impurities are potent mutagens and carcinogens, which can induce genetic mutations, chromosomal rearrangements, or chromosomal breaks to mammalian cell systems . Therefore, it is of importance to monitor their potential presence as trace level impurities in every step of drug development .…”

Section: Introductionmentioning

confidence: 99%

“…These potential Abbreviations: API, active pharmaceutical ingredient; DDTC, N,N-diethyldithiocarbamate; DMA, N,N-dimethylacetamide; EMS, ethyl methanesulfonate; MMS, methyl methanesulfonate; MSA, methanesulfonic acid Conflict of interest: The authors declare no potential conflict of interest. genotoxic impurities are potent mutagens and carcinogens, which can induce genetic mutations, chromosomal rearrangements, or chromosomal breaks to mammalian cell systems [2,3]. Therefore, it is of importance to monitor their potential presence as trace level impurities in every step of drug development [4].…”

Section: Introductionmentioning

confidence: 99%

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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“…Nowadays, chromatographic techniques have exhibited powerful and excellent analytical performance in various fields, such as food inspection , medicine analysis , environmental monitoring , and life science . However, it is very difficult for direct chromatographic analysis of PFCs in complex environmental samples, considering the existence of multiple interfering substances.…”

Section: Introductionmentioning

confidence: 99%

Facile and robust dual interaction modification of hexadecyldimethyl amine magnetic nanoparticles for the ultrasensitive analysis of perfluorinated compounds in environmental water

Liang

Zou

Liu

et al. 2015

J of Separation Science

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In this work, a novel extraction and enrichment technique based on hexadecyldimethyl amine functionalized magnetic nanoparticles has been successfully developed for the preconcentration and ultrasensitive detection of perfluorinated compounds in environmental water samples with high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry. As a novel surfactant, hexadecyldimethyl amine functionalized on magnetic nanoparticles was realized through one-step facile and robust quaterization reaction, greatly superior to previous multiple-step and unstable modification. The functional nanoparticles of homogeneous nanospheres and excellent magnetic properties were characterized with scanning electron microscopy, X-ray diffraction patterns, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. Dual mechanisms of both hydrophobic and electrostatic interactions were simultaneously introduced for anionic perfluorinated compounds effective enrichment. Under optimized extraction conditions, satisfactory precision and accuracy for anionic perfluorinated compounds analysis were achieved with good linear ranging from 0.5 to 20 ng/L, as well as fascinating sensitivity with low limits of detection up to 3.0 × 10(-2) -5.0 × 10(-2) ng/L. High preconcentration efficiency and extraction recoveries ranged from 81.04-103.2% with relative standard deviations (n = 5) less than 10% have also been realized. Thereby, our proposed method is convenient and efficient for enrichment, exhibiting good application prospect in future environmental perfluorinated compounds analysis.

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Determination of trace level genotoxic impurities in small molecule drug substances using conventional headspace gas chromatography with contemporary ionic liquid diluents and electron capture detection

Cited by 48 publications

References 34 publications

Volatile sampling by headspace techniques

Volatile sampling by headspace techniques

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

Facile and robust dual interaction modification of hexadecyldimethyl amine magnetic nanoparticles for the ultrasensitive analysis of perfluorinated compounds in environmental water

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