Use of high-performance liquid chromatographic and microbiological analyses for evaluating the presence or absence of active metabolites of the antifungal posaconazole in human plasma

Kim, Hong; Kumari, Pramila; Laughlin, Mark; Hilbert, Mary Jane; Indelicato, Stephen R.; Lim, Josephine; Lin, Chin‐Chung; Nomeir, Amin A.

doi:10.1016/s0021-9673(02)01599-6

Cited by 42 publications

(26 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several HPLC methods for the quantitation of posaconazole in human plasma employing ultraviolet detection have been described previously (14)(15)(16). These methods require laborious sample preparation along with extensive chromatographic run times.…”

Section: Discussionmentioning

confidence: 99%

A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry

Vogeser

Rieger²,

Ostermann³

et al. 2009

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Background: Posaconazole is now widely used for prophylaxis of invasive fungal infections in immunocompromised patients. The pharmacokinetic properties of the drug argue for therapeutic monitoring, but so far described analytical methods have shortcomings with respect to application in a routine setting. The aim of our work was to develop an analytical method suitable for routine use. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. For sample preparation, protein precipitation followed by on-line solid phase extraction was used. SCH 56984, a posaconazole related compound provided by the manufacturer of posaconazole, was used as internal standard.

show abstract

Section: Discussionmentioning

confidence: 99%

A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry

Vogeser

Rieger²,

Ostermann³

et al. 2009

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…Posaconazole is excreted largely unchanged; there are no active metabolites 88 and the metabolites seen in urine are glucuronide conjugates, 89 produced by UGT1A4. 90 Genetic variants occur in the alleles for this enzyme, 91 some of which cause reduced catalytic activity.…”

Section: Anidulafunginmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

View full text Add to dashboard Cite

“…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%

“…No evidence was found for formation of pharmacologically active metabolites of posaconazole (21). Posaconazole is metabolized essentially via glucuronidation by UDP-glucuronosyltransferase, resulting in mono-and di-glucuronides as the primary metabolites in plasma (25,30).…”

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

View full text Add to dashboard Cite

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-

show abstract

Use of high-performance liquid chromatographic and microbiological analyses for evaluating the presence or absence of active metabolites of the antifungal posaconazole in human plasma

Cited by 42 publications

References 9 publications

A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry

A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

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

Contact Info

Product

Resources

About