Structural characterization of the oxidative degradation products of an antifungal agent SCH 56592 by LC–NMR and LC–MS

Feng, Wenqing; Liu, Haiying; Chen, Guodong; Malchow, R. D.; Bennett, Frank; Lin, Elizabeth Z.; Pramanik, Birendra N.; Chan, Tze-Ming

doi:10.1016/s0731-7085(00)00522-7

Cited by 47 publications

(19 citation statements)

References 23 publications

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“…Moreover, standardization of assays for posaconazole quantification is another issue to be addressed. Various HPLC assays for quantification of posaconazole have been reported, applying either UV detection (11,21,22), fluorescence detection (FLD) (23) or mass spectrometric detection (LC-MS) (24)(25)(26)(27)(28)(29). However, inter-laboratory comparisons of different posaconazole assays have not been reported at present, and there is currently only limited availability of proficiency testing schemes.…”

Section: Introductionmentioning

confidence: 99%

Impact of glucuronide interferences on therapeutic drug monitoring of posaconazole by tandem mass spectrometry

Krüger

Vogeser

Burghardt³

et al. 2010

Clinical Chemistry and Laboratory Medicine

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Background: Posaconazole is a novel antifungal drug for oral application intended especially for therapy of invasive mycoses. Due to variable gastrointestinal absorption, adverse side effects, and suspected drug-drug interactions, therapeutic drug monitoring (TDM) of posaconazole is recommended. Method: A fast ultra performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) method for quantification of posaconazole with a run-time -3 min was developed and compared to a LC-MS/MS method and HPLC method with fluorescence detection. Results: During evaluation of UPLC-MS/MS, two earlier eluting peaks were observed in the MRM trace of posaconazole. This was only seen in patient samples, but not in spiked calibrator samples. Comparison with LC-MS/MS disclosed a significant bias with higher concentrations measured by LC-MS/MS, while UPLC-MS/MS showed excellent agreement with the commercially available HPLC method. In the LC-MS/MS procedure, comparably wide and left side shifted peaks were noticed. This could be ascribed to insource fragmentation of conjugate metabolites during electrospray ionisation. Precursor and product ion scans confirmed the assumption that the additional compounds are posaconazole glucuronides. Reducing the cone voltage led to disappearance of the glucuronide peaks. Slight modification of the LC-MS/MS method enabled separation of the main interference, leading to significantly reduced deviation. Conclusions: These results highlight the necessity to reliably eliminate interference from labile drug metabolites for cor-

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Section: Introductionmentioning

confidence: 99%

Impact of glucuronide interferences on therapeutic drug monitoring of posaconazole by tandem mass spectrometry

Krüger

Vogeser

Burghardt³

et al. 2010

Clinical Chemistry and Laboratory Medicine

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“…LC/NMR has only recently overcome the sensitivity limitations historically impeding its widespread application in the pharmaceutical industry. [116][117][118][119][120][121][122] For example, LC/ NMR with a cryo probe (as described in the example below) has approximately four times better signal-tonoise ratio than a regular probe. Therefore, although about 0.5 mg sample is needed for a regular probe to detect Carbon-NMR signals, the cryo probe requires only 0.1 mg of samples.…”

Section: Nmr and Lc/nmr For Structure Identification And Confirmationmentioning

confidence: 99%

Identification of Pharmaceutical Impurities in Formulated Dosage Forms

Pan

Liu

Motto

2011

Journal of Pharmaceutical Sciences

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“…There had been numerous reports in the literature that involved LC/MS and LC/MS/MS for characterization of degradation products [1, [88][89][90][91][92][93][94][95][96][97]. An early example of the rapid structure elucidation of drug degradants induced by acid, base and heat by LC/MS was reported by Rourick et al in 1996 [90].…”

Section: Characterization Of Decomposition Products By Lc/msmentioning

confidence: 99%

“…The same group demonstrated that the similar procedure could be applied to obtain the structural information of the degradation products of paclitaxel (Taxol) [89]. Recently, Feng et al [92] investigated the oxidative degradation products of an antifungal agent, SCH 56592 (Scheme 7), by both LC/MS and LC/NMR analysis. Four major oxidative degradation products of SCH 56592 were characterized, and the oxidation was found to be occurred at the piperazine ring in the center of the drug molecule.…”

Section: Characterization Of Decomposition Products By Lc/msmentioning

confidence: 99%