Universal response model for a corona charged aerosol detector

Hutchinson, Joseph P.; Li, Jianfeng; Farrell, William; Groeber, Elizabeth; Szücs, Roman; Dicinoski, Greg W.; Haddad, Paul R.

doi:10.1016/j.chroma.2010.09.056

Cited by 69 publications

(40 citation statements)

References 27 publications

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“…The absence of nitrogen atoms in the structure of β-274 artemether renders the CLND technique useless, as the response is directly proportional to the 275 nitrogen content [25][26][27]. The ELSD and CAD techniques record only non-or semi-volatile 276 compounds after evaporation of column eluent, often with inherent sensor noise and drift, 277 being sensitive to the mobile phase composition [28][29][30]. 278…”

Section: Page 8 Of 23mentioning

confidence: 99%

Relative response factor determination of β-artemether degradants by a dry heat stress approach

Spiegeleer

D׳Hondt

Vangheluwe

et al. 2012

Journal of Pharmaceutical and Biomedical Analysis

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Relative response factor determination of rmbeta-artemether degradants by a dry heat stress approach, Journal of Pharmaceutical and Biomedical Analysis (2010), doi:10.1016/j.jpba.2012 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. During the stability evaluation of -artemether containing finished drug products, a consistent 20 and disproportional increase in the UV-peak areas of -artemether degradation products, 21 when compared to the peak area decline of -artemether itself, was observed. This suggested 22 that the response factors of the formed -artemether degradants were significantly higher than 23 β-artemether. Dry heat stressing of -artemether powder, as a single compound, using 24 different temperatures (125 °C -150 °C), times (10 min -90 min) and environmental 25 conditions (neutral, KMnO 4 and zinc), resulted in the formation of 17 degradants. The vast 26 majority of degradants seen during the long-term and accelerated ICH stability study of the 27 drug product, were also observed here. The obtained stress results allowed the calculation of 28 the overall average relative response factor (RRF) of -artemether degradants, i.e. 21.2, 29 whereas the individual RRF values of the 9 most prominent selected degradants ranged from 30 4.9 to 42.4. Finally, Ames tests were performed on -artemether as well as a representative 31 stressed sample mixture, experimentally assessing their mutagenic properties. Both were 32 found to be negative, suggesting no mutagenicity problems of the degradants at high 33 concentrations. Our general approach and specific results solve the developmental quality 34 issue of mass balance during stability studies and the related genotoxicity concerns of the key 35 antimalarial drug -artemether and its degradants. 36

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Section: Page 8 Of 23mentioning

confidence: 99%

Relative response factor determination of β-artemether degradants by a dry heat stress approach

Spiegeleer

D׳Hondt

Vangheluwe

et al. 2012

Journal of Pharmaceutical and Biomedical Analysis

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“…2b). Hutchinson et al [18] reported maximum reliable CAD response at 70% ACN, and recommended this concentration for applications requiring maximum sensitivity. Retention is often poor at this ACN concentration in HILIC; a typical range for HILIC is 70-95% ACN.…”

Section: Calibration Curves (Hplc)mentioning

confidence: 97%

“…1-1000 ppm) CAD response is non-linear, while over narrow ranges of analyte concentration, it is quasi-linear [8]. Using FIA, Hutchinson et al investigated CAD calibration using sucralose, amitriptyline, dibucaine and quinine at concentrations of 1 g/mL to 1 mg/mL (25 L injections) [18]. Although not commented on by the authors, their data suggest a low quasi-linear range below approximately 0.05 mg/mL and an upper quasi-linear linear range between 0.4 and 1.0 mg/mL.…”

Section: Calibration Curves (Hplc)mentioning

confidence: 98%

“…Furthermore, as with other aerosol-based detectors, detector response is dependent on organic solvent content. While changing detector response with organic solvent concentration has been investigated for its detrimental effect on response uniformity in gradient elution [16][17][18], high organic concentrations as used in HILIC may be advantageous for sensitivity as it should facilitate desolvation of particles in the CAD. Aerosol-based detectors are known to produce non-linear calibration curves [19], which can arise for different reasons in different detectors.…”

Section: Introductionmentioning

confidence: 99%

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Performance of charged aerosol detection with hydrophilic interaction chromatography

Russell

Heaton

Underwood

et al. 2015

Journal of Chromatography A

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The performance of the charged aerosol detector (CAD) was investigated using a diverse set of 29 solutes, including acids, bases and neutrals, over a range of mobile phase compositions, particularly with regard to its suitability for use in hydrophilic interaction chromatography (HILIC). Flow injection analysis was employed as a rapid method to study detector performance. CAD response was 'quasi-universal', strong signals were observed for compounds that have low volatility at typical operating (room) temperature. For relatively involatile solutes, response was reasonably independent of solute chemistry, giving variation of 12-18% RSD from buffered 95% ACN (HILIC) to 10% ACN (RP). Somewhat higher response was obtained for basic compared with neutral solutes. For cationic basic solutes, use of anionic reagents of increasing size in the mobile phase (formic, trifluoroacetic and heptafluorobutyric acid) produced somewhat increased detector response, suggesting that salt formation with these reagents is contributory. However, the increase was not stoichiometric, pointing to a complex mechanism. In general, CAD response increased as the concentration of acetonitrile in the mobile phase was increased from highly aqueous (10% ACN) to values typical in the HILIC range (80-95% ACN), with signal to noise ratios about four times higher than those for the RP range. The response of the CAD is non-linear. Equations describing aerosol formation cannot entirely explain the shape of the plots. Limits of detection (determined with a column for solutes of low k) under HILIC conditions were of the order of 1-3ng on column, which compares favourably with other universal detectors. CAD response to inorganic anions allows observation of the independent movement through the column of the cationic and anionic constituents of basic drugs, which appear to be accompanied by mobile phase counterions, even at quite high solute concentrations.

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“…These apparatus can detect the nonvolatile species independent of their chemical structures and are claimed to provide a universal response for the analytes. [9][10] The universal response is a prominent feature that enables us to make quantitative analyses without having to prepare individual calibrations even for newly synthesized or unknown compounds. 1,10 From the comparison of these detectors, 9,[11][12][13] the reproducibility of the response from corona CAD is better than two other detectors.…”

Section: Introductionmentioning

confidence: 99%

Effects of Densities of Brominated Flame Retardants on the Detection Response for HPLC Analysis with a Corona-charged Aerosol Detector

et al. 2015

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Universal response model for a corona charged aerosol detector

Cited by 69 publications

References 27 publications

Relative response factor determination of β-artemether degradants by a dry heat stress approach

Relative response factor determination of β-artemether degradants by a dry heat stress approach

Performance of charged aerosol detection with hydrophilic interaction chromatography

Effects of Densities of Brominated Flame Retardants on the Detection Response for HPLC Analysis with a Corona-charged Aerosol Detector

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