Ultra-fast quantitation of voriconazole in human plasma by coated blade spray mass spectrometry

2017-09-10
Tascon, Marcos
Gomez-Rios, German Augusto
Reyes-Garces, Nathaly
Poole, Justen
Boyacı, Ezel
Pawliszyn, Janusz
Voriconazole is a triazole broad-spectrum antifungal medication often used to treat fungal infections caused by Aspergillus and Fusarium species. One of the main challenges associated with the implementation of this medication is its narrow therapeutic concentration range, demonstrating toxicity at concentrations above 6 mu g/mL and limited efficacy at concentrations below 2 mu g/mL. As a result, methodologies which permit the rapid and accurate quantitation of voriconazole in patients are highly desirable. In this work two different approaches based on coated blade spray directly coupled to mass spectrometry (CBS-MS) are introduced; each enabling the quantitation of voriconazole in plasma samples with a simple and fast sample preparation and no chromatographic step. The first approach involves a rapid extraction (1 min) of the target analyte from 300 mu L of human plasma using conventional laboratory vessels (e.g. vial, 96-well plate). Alternatively, the second strategy consists of a 2 min extraction from a plasma droplet (10 mu L) placed on the coated area of the blade. Both procedures were successfully validated and good linearity (R-2 >= 0.998), accuracy (91-122%) and precision (<8%) were attained in the concentration range evaluated (0.1-50 mu g/mL). Moreover, very good results in terms of relative matrix effects were obtained given that the slopes of the calibration curves constructed in five different plasma lots exhibited relative standard deviation (RSD) values below 7%. Herein we demonstrated that CBS-MS is a technology suitable for the ultra-fast determination of voriconazole in human plasma samples. Indeed, the proposed methodology can be easily used either for routine drug monitoring or for in vitro pharmacokinetic studies in applications where very small sample volumes are available and great temporal resolution is needed.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Suggestions

Identification of the new immunogenic proteins of bordetella pertussis by immunoproteomics
Altındiş, Emrah; Özcengiz, Gülay; Department of Biotechnology (2007)
The genus Bordetella contains several pathogenic species generally associated with upper respiratory tract infections in warm-blooded animals. Bordetella pertussis is the etiologic agent of whooping cough. Whooping cough is presently one of the ten most common causes of death from infectious diseases and reported by the World Health Organisation (WHO) to cause 50 million cases and 350000 deaths worldwide per year, mainly among unvaccinated individuals in poor countries. The term proteome, in analogy to the ...
Characterization and analysis of the antioxidant capacity of functional phenolics oxidized by Scytalidium thermophilum catalase phenol oxidase (CATPO)
Söyler, Ulviye Betül; Ögel, Zümrüt Begüm; Şensoy, İlkay; Department of Food Engineering (2012)
Scytalidium thermophilum is a termophilic fungus that effectively produces the extracellular enzyme catalase phenol oxidase (CATPO). The enzyme is distinct among catalases with its bifunctionality of oxidising phenolic compounds in the absence of H2O2. CATPO is capable of oxidizing catechol, chlorogenic acid, caffeic acid and catechin which are ortho –diphenolic compounds. Diphenolic compounds are known as strong antioxidants. Catalase is one of the important antioxidant enzymes. Therefore, in this thesis t...
Dynamic analysis of secretome alterations in a bacilysin-knock out mutant of bacillus subtilis
Tekin İşlerel, Elif; Özcengiz, Gülay; Department of Biology (2017)
The members of the genus Bacillus produce a wide variety of secondary metabolites with antimetabolic and pharmacological activities. Bacilysin, being produced and excreted by certain strains of B. subtilis, is a dipeptide antibiotic composed of L-alanine and L-anticapsin which is synthesized enzymatically. As shown earlier by our research group, the expression of bacilysin biosynthetic operon (bacA) is relatively constant during the exponential growth, but increases during the transition between exponential...
The contribution of kinetoplast DNA to Leishmania major experimental infection and evaluation of Leishmania extracellular vesicle based vaccine against cutaneous Leishmaniasis in BALB/C mice
Ayanoğlu, İhsan Cihan; Gürsel, Mayda; Department of Biology (2019)
Cutaneous Leishmaniasis (CL) is a neglected vector borne parasitic infection that manifests as self-healing skin lesions or cause debilitating large chronic or recurring lesions. CL is endemic in Turkey and its incidence rate is on the rise due to immigration of refugees from affected regions. Leishmania parasites harbor a unique mitochondrial DNA structure called kinetoplast DNA (kDNA), consisting of giant networks of catenated mini and maxi-circles. The role of kDNA in infection is poorly understood. In t...
Development of recombinant vaccines composed of PlpE and OmpH from pasteurella multocida A:3
Okay, Sezer; Özcengiz, Gülay; Department of Biology (2011)
Pasteurella multocida serotype A:3 is a gram-negative bacterial pathogen which is one of the causative agents of shipping fever in cattle. In this study, ompH and two fragments of plpE gene (plpEN and plpEC) were cloned from the genomic DNA of P. multocida P-1062 (ATCC 15743, serotype A:3) and plpEN-ompH and plpEC-ompH fusions were constructed. In vitro expression of the genes was shown in HEK-293 cells. Later, full-length plpE gene was cloned and the recombinant proteins were expressed in E. coli and purif...
Citation Formats
M. Tascon, G. A. Gomez-Rios, N. Reyes-Garces, J. Poole, E. Boyacı, and J. Pawliszyn, “Ultra-fast quantitation of voriconazole in human plasma by coated blade spray mass spectrometry,” JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, pp. 106–111, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/39048.