Mass spectral studies on aminocyclitol–aminoglycoside antibiotics

Daniels, Peter J. L.; Mallams, Alan K.; Weinstein, Jay; Wright, John J.; Milne, G. W. A.

doi:10.1039/p19760001078

Cited by 31 publications

(12 citation statements)

References 2 publications

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“…The AG class of compounds consists of an aminocyclitol moiety with two or more amino sugar rings [ 29 ]. A characteristic quaternary ammonium group makes AGs polycationic (positive charge) and highly polar [ 30 , 31 ].…”

Section: Pharmacokinetics and Antimicrobial Mechanism Of Aminoglycmentioning

confidence: 99%

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Huth

Ricci

Cheng

2011

International Journal of Otolaryngology

332

302

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Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.

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Section: Pharmacokinetics and Antimicrobial Mechanism Of Aminoglycmentioning

confidence: 99%

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Huth

Ricci

Cheng

2011

International Journal of Otolaryngology

332

302

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“…A fragmentation pathway for paromomycin was previously proposed by Li et al based on data obtained with an ion trap mass spectrometer . In this study, the paromomycin reference standard was analyzed by ESI‐QTOF and the resulting product ions compared with reported literature for paromomycin and other structurally related aminoglycosides to create a modified paromomycin fragmentation pathway (see Scheme S1, supporting information) for comparison of unknown impurity data. The paromomycin I peak yielded a [M + H] + base peak at m/z 616, a sodium adduct at m/z 638, and a potassium adduct at m/z 654, as well as in‐source fragmentation.…”

Section: Resultsmentioning

confidence: 99%

“…Impurities observed during HPLC/CAD analysis at levels above a 0.7% peak area threshold established on the basis of the ICH Q3B(R2) guidelines were subjected to further investigation by LC/ MS/MS. Six HPLC/CAD impurity peaks (peaks 3, 5, 6,7,8,9) met or exceeded the ICH Q3B(R2) threshold value for peak identification.…”

Section: Lc/ms Of the Unknown Impuritiesmentioning

confidence: 99%

Investigation of unknown impurities of paromomycin in a 15% topical cream by liquid chromatography combined with mass spectrometry

Hertzler¹,

Knuth²,

Preston³

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale Characterization of unknown impurities in degraded paromomycin 15% topical cream samples by ultra‐high‐performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) gas‐phase fragmentation is described. Methods A volatile reversed‐phase high‐performance liquid chromatography/charged aerosol detection (RP‐HPLC/CAD) method was developed and validated for fast and consistent analysis of the paromomycin potency and impurity values in drug substance and drug product samples. A Veo charged aerosol detector was chosen for routine analysis. The method shows separation of two paromomycin isomers as well as twelve unknown impurity peaks. The identity of the unknown impurities was investigated by LC/MS/MS using a quadrupole time‐of‐flight (QTOF) mass spectrometer. Results Six of the HPLC/CAD impurity peaks met the ICH Q3B(R2) threshold for identification and were investigated by coupling the developed LC method with a QTOF instrument. Structures for the impurities were proposed based on gas‐phase fragmentation patterns of the paromomycin reference standard. Impurity fragmentation pathways were proposed based on literature of other structurally related aminoglycoside compounds. Conclusions Nine unknown paromomycin impurities were identified and the observed modifications included acetylation, carbamylation, gain of a hexose, and loss of glucosamine. The most abundant paromomycin modification was carbamylation by urea (a cream excipient) characterized by a 43 Da mass increase.

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“…To date, the most common methods used for detection and characterization of the aminoglycoside antibiotics and their complexes include 1 H NMR spectroscopy,3 derivatization for high‐performance liquid chromatographic analysis with UV detection analysis4–6 and mass spectrometry (MS) 7–17. A few examples of MS studies include early electron ionization work by Daniels et al 15 and Ohashi et al 17 for the analysis of numerous underivatized aminoglycosides. Ling et al recently performed experiments to quantify several antibiotics (including aminoglycosides) using matrix‐assisted laser desorption/ionization,9 while liquid chromatography (LC) coupled to ionspray was utilized to detect and quantify aminoglycosides in various biological matrices such as kidney tissue 7.…”

Section: Introductionmentioning

confidence: 99%

Analysis of protonated and alkali metal cationized aminoglycoside antibiotics by collision-activated dissociation and infrared multi-photon dissociation in the quadrupole ion trap

Goolsby

Brodbelt

2000

J. Mass Spectrom.

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Nine aminoglycoside antibiotics were analyzed in two quadrupole ion trap mass spectrometers using electrospray ionization. Structural information was obtained via collision-activated dissociation (CAD) and infrared multi-photon dissociation (IRMPD) of the protonated species. Several of the compounds, having multiple basic sites, preferred the doubly protonated form while some existed in the singly charged state or were distributed between single and doubly protonated species, allowing comparison of the fragmentation patterns of the two charge states. In general, IRMPD is as efficient as CAD, produces more low-mass fragment ions, and is more universally applied owing to its low dependence on trapping, pressure and tuning conditions. Alkali metal complexation using Li(+) and Na(+) was probed as a means of producing different fragmentation patterns, but in most cases the resulting fragmentation patterns were simplified versions of those obtained for the protonated analogs.

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Mass spectral studies on aminocyclitol–aminoglycoside antibiotics

Cited by 31 publications

References 2 publications

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Investigation of unknown impurities of paromomycin in a 15% topical cream by liquid chromatography combined with mass spectrometry

Analysis of protonated and alkali metal cationized aminoglycoside antibiotics by collision-activated dissociation and infrared multi-photon dissociation in the quadrupole ion trap

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