Direct Detection of a Sulfonate Ester Genotoxic Impurity by Atmospheric-Pressure Thermal Desorption–Extractive Electrospray–Mass Spectrometry

Devenport, Neil A.; Sealey, Laura C.; Alruways, Faisal H.; Weston, Daniel J.; Reynolds, James C.; Creaser, Colin S.

doi:10.1021/ac401054n

Cited by 23 publications

(14 citation statements)

References 24 publications

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“…The direct detection of volatile potentially genotoxic impurities by thermal desorption EESI combined with MS and IMS-MS has also been reporte. 8 , 9 Coupling a gas chromatograph to an electrospray mass spectrometer has also been accomplished adding in a hyphenated separation to resolve complex mixtures. This was demonstrated using a multiple channel (7 emitter) ESI source in 1998, 10 here the GC outlet was directed into the central electrospray emitter enabling eluted analytes to interact with the solvent before being electrosprayed.…”

Section: Introductionmentioning

confidence: 99%

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface

Reynolds¹,

Jimoh²,

Guallar-Hoyas³

et al. 2014

J. Breath Res.

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A two-stage thermal desorption/secondary electrospray ionization/time-of-flight mass spectrometry for faster targeted breath profiling has been studied. A new secondary electrospray ionization (SESI) source was devised to constrain the thermal desorption plume and promote efficient mixing in the ionization region. Further, a chromatographic pre-separation stage was introduced to suppress interferences from siloxanes associated with thermal desorption profiles of exhaled breath samples. In vitro tests with 5-nonanone indicated an increased sensitivity and a lowered limit-of-detection, both by a factor of ~4, the latter to an on-trap mass of 14.3 ng, equivalent to a sampled breath concentration of 967 pptv. Analysis of the mass spectrometric responses from 20 breath samples acquired sequentially from a single participant indicated enhanced reproducibility (reduced relative standard deviations (RSD) for 5-nonanone, benzaldehyde and 2-butanone were 28 %, 16% and 14% respectively. The corresponding values for an open SESI source were that 5-nonanone was not detected, with %RSD of 39% for benzaldehyde and 31% for 2-butanone). The constrained source with chromatographic pre-separation resulted in an increase in the number of detectable volatile organic compounds (VOCs) from 260 mass spectral peaks with an open SESI source to 541 peaks with the constrained source with pre-separation. Most of the observed VOCs were present at trace levels, at less than 2.5% of the intensity of the base peak. Seventeen 2.5 dm3 distal breath samples were collected from asthma patients and healthy controls respectively, and subjected to comparative high-throughput screening using thermal desorption/SESI/time-of-flight mass spectrometry (TD-SESI-ToFMS). Breath metabolites were detected by using a background siloxane ion (hexamethylcyclotrisiloxane m/z 223.0642) as an internal lockmass. Eleven breath metabolites were selected from the breath research literature and successfully targeted. These data reinforce the proposition that TD-SESI-MS has potential for development as a rapid screening method for disease stratification and targeted metabolism profiling.

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Section: Introductionmentioning

confidence: 99%

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface

Reynolds¹,

Jimoh²,

Guallar-Hoyas³

et al. 2014

J. Breath Res.

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“…24 The TD probe was constructed by placing a cylindrical heater cartridge (2.5 mm o.d. × 50 mm; RS Components Ltd., Northants, UK) into a stainless steel tube (12 i.d.…”

Section: Experimental Sectionmentioning

confidence: 99%

Direct Determination of Urinary Creatinine by Reactive-Thermal Desorption-Extractive Electrospray-Ion Mobility-Tandem Mass Spectrometry.

et al. 2013

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A direct, ambient ionization method has been developed for the determination of creatinine in urine that combines derivatization and thermal desorption with extractive electrospray ionization and ion mobility-mass spectrometry. The volatility of creatinine was enhanced by a rapid on-probe aqueous acylation reaction, using a custom-made thermal desorption probe, allowing thermal desorption and ionization of the monoacylated derivative. The monoacyl creatinine [M + H]+ ion (m/z 156) was subjected to mass-to-charge selection and collision induced dissociation to remove the acyl group, generating the protonated creatinine [M + H]+ product ion at m/z 114 before an ion mobility separation was applied to reduce chemical noise. Stable isotope dilution using creatinine-d3 as internal standard was used for quantitative measurements. The direct on-probe derivatization allows high sample throughput with a typical cycle time of 1 min per sample. The method shows good linearity (R2 = 0.986) and repeatability (%RSD 8–10%) in the range of 0.25–2.0 mg/mL. The creatinine concentrations in diluted urine samples from a healthy individual were determined to contain a mean concentration of 1.44 mg/mL creatinine with a precision (%RSD) of 9.9%. The reactive ambient ionization approach demonstrated here has potential for the determination of involatile analytes in urine and other biofluids.

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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 .…”

Section: Introductionmentioning

confidence: 99%

“…The ability to control potential genotoxic impurities at low concentrations in active pharmaceutical ingredients (APIs) is vital in the development of APIs [1]. 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.…”

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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Direct Detection of a Sulfonate Ester Genotoxic Impurity by Atmospheric-Pressure Thermal Desorption–Extractive Electrospray–Mass Spectrometry

Cited by 23 publications

References 24 publications

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface

Analysis of human breath samples using a modified thermal desorption: gas chromatography electrospray ionization interface

Direct Determination of Urinary Creatinine by Reactive-Thermal Desorption-Extractive Electrospray-Ion Mobility-Tandem Mass Spectrometry.

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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