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Oskar Gonzalez
FARMARTEM Group, Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain

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Journal article
Published: 06 July 2021 in Microchemical Journal
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Fumagillin is a biomolecule produced by Aspergillus fumigatus that is gaining relevance due to its connection with invasive aspergillosis. The determination of this molecule might help to understand the propagation of this disease and study its use as a potential biomarker. In spite of the interest of fumagillin in microbiological research, no quantitative method has been developed so far for its determination in cell culture media. In this work, the first validated method for the quantitative analysis of fumagillin in RPMI-1640 is presented. The sample treatment consists of a mixed-mode anion exchange Solid Phase Extraction that effectively removes potential interferences and offered a recovery of 83 ± 7%. The analysis was carried out by Ultra High Performance Liquid Chromatography coupled to Diode Array Detection at 336 nm. The method fulfilled the validation criteria established by EMA and FDA guidelines for bioanalysis (selectivity, carry over, linearity, accuracy, precision, dilution integrity and stability) and offers a limit of quantitation (25 μg·L−1) suitable for its intended use. Indeed, the method was satisfactorily applied to the quantification of the fumagillin produced by three strains of Aspergillus fumigatus with different toxin production capacity.

ACS Style

Oskar González; Ane Yaldebere; Xabier Guruceaga; Andoni Ramírez-García; Aitor Rementeria; Rosa María Alonso. A novel SPE-UHPLC-DAD method for the determination of fumagillin produced by Aspergillus fumigatus in cell culture media. Microchemical Journal 2021, 169, 106605 .

AMA Style

Oskar González, Ane Yaldebere, Xabier Guruceaga, Andoni Ramírez-García, Aitor Rementeria, Rosa María Alonso. A novel SPE-UHPLC-DAD method for the determination of fumagillin produced by Aspergillus fumigatus in cell culture media. Microchemical Journal. 2021; 169 ():106605.

Chicago/Turabian Style

Oskar González; Ane Yaldebere; Xabier Guruceaga; Andoni Ramírez-García; Aitor Rementeria; Rosa María Alonso. 2021. "A novel SPE-UHPLC-DAD method for the determination of fumagillin produced by Aspergillus fumigatus in cell culture media." Microchemical Journal 169, no. : 106605.

Journal article
Published: 13 February 2021 in Molecules
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Insect plagues are a problem often hard to solve due to the harmful effects caused by the pesticides used to combat them. Consequently, the pesticide market is increasingly trying to develop new technologies to prevent the unwanted effects that common plague treatments usually bring with them. In this work, four specific bioattractants of Musca domestica, extracted from fungi (β-ocimene, phenol, p-cresol, and indole) were microencapsulated with β-cyclodextrin in order to produce an economically and environmentally sustainable bait containing biocides in the near future. Cyclodextrins will retain these volatile compounds until their use by the consumer when the product comes into contact with water. Then, the bioattractants will be released in the medium in a controlled manner. An analytical methodology based on headspace extraction coupled to gas chromatography and mass spectrometry (HS-GC/MS) has been developed and validated following Environmental Protection Agency (EPA) and European Commission Directorate General for Health and Food Safety guidelines for the bioattractants controlled release study from the microencapsulated product. The analytical method has been shown to be accurate and precise and has the sensitivity required for controlled release studies of the four bioattractants analyzed. The release of the bioattractants from microencapsulated products achieved the “plateau” after 3 h in all cases.

ACS Style

María Luz Alonso; Oscar González; Rosa María Alonso. Optimization and Validation of HS-GC/MS Method for the Controlled Release Study of Microencapsulated Specific Bioattractants for Target-Plaguicide Production. Molecules 2021, 26, 996 .

AMA Style

María Luz Alonso, Oscar González, Rosa María Alonso. Optimization and Validation of HS-GC/MS Method for the Controlled Release Study of Microencapsulated Specific Bioattractants for Target-Plaguicide Production. Molecules. 2021; 26 (4):996.

Chicago/Turabian Style

María Luz Alonso; Oscar González; Rosa María Alonso. 2021. "Optimization and Validation of HS-GC/MS Method for the Controlled Release Study of Microencapsulated Specific Bioattractants for Target-Plaguicide Production." Molecules 26, no. 4: 996.

Paper
Published: 13 August 2020 in The Analyst
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Plasma is a potential surrogate matrix for liver and the statistical combination of both matrices helps to better understand the differences in metabolic profiles among study groups of different ages.

ACS Style

Oihane E. Albóniga; Oskar González; Rosa M. Alonso; Yun Xu; Royston Goodacre. Comparison of liver and plasma metabolic profiles in piglets of different ages as animal models for paediatric population. The Analyst 2020, 145, 6859 -6867.

AMA Style

Oihane E. Albóniga, Oskar González, Rosa M. Alonso, Yun Xu, Royston Goodacre. Comparison of liver and plasma metabolic profiles in piglets of different ages as animal models for paediatric population. The Analyst. 2020; 145 (21):6859-6867.

Chicago/Turabian Style

Oihane E. Albóniga; Oskar González; Rosa M. Alonso; Yun Xu; Royston Goodacre. 2020. "Comparison of liver and plasma metabolic profiles in piglets of different ages as animal models for paediatric population." The Analyst 145, no. 21: 6859-6867.

Journal article
Published: 23 May 2020 in Journal of Pharmaceutical and Biomedical Analysis
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The actual scenario in the fight against fungal infections forces researchers to carry through with resistance studies to improve the therapies. These studies, which are performed in cell culture media, need accurate and sensitive analytical methodologies. That is why, in this work, an analytical method for caspofungin (CSF) concentration determination in RPMI-1640 cell culture medium with on-line sample treatment was developed and validated. CSF concentration was determined by HPLC-FLD using a column-switching procedure. The chromatographic analysis was carried out in less than 10 min using a C8 column (4 × 4 mm, 5 μm) as extraction stationary phase and a HSS T3 column (4.6 × 100 mm, 5 μm) as the analytical column. The used mobile phases were mixtures of phase A: pH 2 (adjusted with TFA) aqueous phase and phase B: ACN. For the extraction, the composition was (95:5, A:B v/v) and for the analysis (60:40, A:B v/v), both done in isocratic elution mode. These chromatographic conditions allowed reaching a limit of quantification of 10 μg/L, using 100 μL of sample with an injected volume of 40 μL. The proposed method was successfully validated in terms of selectivity, carryover, linear concentration range, accuracy and precision according to the criteria established by the Food and Drug Administration. Available amount of CSF in RPMI-1640 solution was found critical. CSF concentrations remained stable up to 2 h at room temperature. The developed method was applied for the direct analysis of CSF concentrations from in vitro experiments in presence of C. glabrata (CAGL18). The results highlight the decrease of cell proliferation even if the CSF amount decreases too, which asks question about the real value of the efficient concentration for CSF antifungal activity.

ACS Style

B. Uribe; Oskar Gonzalez; Isabelle Ourliac-Garnier; P. Le Pape; B.B. Ba; R.M. Alonso; K. Gaudin. Determination of antifungal caspofungin in RPMI-1640 cell culture medium by column-switching HPLC-FLD. Journal of Pharmaceutical and Biomedical Analysis 2020, 188, 113366 .

AMA Style

B. Uribe, Oskar Gonzalez, Isabelle Ourliac-Garnier, P. Le Pape, B.B. Ba, R.M. Alonso, K. Gaudin. Determination of antifungal caspofungin in RPMI-1640 cell culture medium by column-switching HPLC-FLD. Journal of Pharmaceutical and Biomedical Analysis. 2020; 188 ():113366.

Chicago/Turabian Style

B. Uribe; Oskar Gonzalez; Isabelle Ourliac-Garnier; P. Le Pape; B.B. Ba; R.M. Alonso; K. Gaudin. 2020. "Determination of antifungal caspofungin in RPMI-1640 cell culture medium by column-switching HPLC-FLD." Journal of Pharmaceutical and Biomedical Analysis 188, no. : 113366.

Original article
Published: 10 January 2020 in Metabolomics
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Several software packages containing diverse algorithms are available for processing Liquid Chromatography-Mass Spectrometry (LC–MS) chromatographic data and within these deconvolution packages different parameters settings can lead to different outcomes. XCMS is the most widely used peak picking and deconvolution software for metabolomics, but the parameter selection can be hard for inexpert users. To solve this issue, the automatic optimization tools such as Isotopologue Parameters Optimization (IPO) can be extremely helpful. To evaluate the suitability of IPO as a tool for XCMS parameters optimization and compare the results with those manually obtained by an exhaustive examination of the LC–MS characteristics and performance. Raw HPLC-TOF–MS data from two types of biological samples (liver and plasma) analysed in both positive and negative electrospray ionization modes from three groups of piglets were processed with XCMS using parameters optimized following two different approaches: IPO and Manual. The outcomes were compared to determine the advantages and disadvantages of using each method. IPO processing produced the higher number of repeatable (%RSD < 20) and significant features for all data sets and allowed the different piglet groups to be distinguished. Nevertheless, on multivariate level, similar clustering results were obtained by Principal Component Analysis (PCA) when applied to IPO and manual matrices. IPO is a useful optimization tool that helps in choosing the appropriate parameters. It works well on data with a good LC–MS performance but the lack of such adequate data can result in unrealistic parameter settings, which might require further investigation and manual tuning. On the contrary, manual selection criteria requires deeper knowledge on LC–MS, programming language and XCMS parameter interpretation, but allows a better fine-tuning of the parameters, and thus more robust deconvolution.

ACS Style

Oihane E. Albóniga; Oskar Gonzalez; Rosa M. Alonso; Yun Xu; Royston Goodacre. Optimization of XCMS parameters for LC–MS metabolomics: an assessment of automated versus manual tuning and its effect on the final results. Metabolomics 2020, 16, 14 .

AMA Style

Oihane E. Albóniga, Oskar Gonzalez, Rosa M. Alonso, Yun Xu, Royston Goodacre. Optimization of XCMS parameters for LC–MS metabolomics: an assessment of automated versus manual tuning and its effect on the final results. Metabolomics. 2020; 16 (1):14.

Chicago/Turabian Style

Oihane E. Albóniga; Oskar Gonzalez; Rosa M. Alonso; Yun Xu; Royston Goodacre. 2020. "Optimization of XCMS parameters for LC–MS metabolomics: an assessment of automated versus manual tuning and its effect on the final results." Metabolomics 16, no. 1: 14.

Review
Published: 20 December 2019 in Toxins
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Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses through the production of secondary metabolites, including several mycotoxins (gliotoxin, fumagillin, pseurotin A, etc.) also seem to play an important role in causing these infections. Since the discovery of the A. fumigatus fumagillin in 1949, many studies have focused on this toxin and in this review we gather all the information currently available. First of all, the structural characteristics of this mycotoxin and the different methods developed for its determination are given in detail. Then, the biosynthetic gene cluster and the metabolic pathway involved in its production and regulation are explained. The activity of fumagillin on its target, the methionine aminopeptidase type 2 (MetAP2) enzyme, and the effects of blocking this enzyme in the host are also described. Finally, the applications that this toxin and its derivatives have in different fields, such as the treatment of cancer and its microsporicidal activity in the treatment of honeybee hive infections with Nosema spp., are reviewed. Therefore, this work offers a complete review of all the information currently related to the fumagillin mycotoxin secreted by A. fumigatus, important because of its role in the fungal infection process but also because it has many other applications, notably in beekeeping, the treatment of infectious diseases, and in oncology.

ACS Style

Xabier Guruceaga; Uxue Perez-Cuesta; Ana Abad-Diaz De Cerio; Oskar Gonzalez; Rosa M. Alonso; Fernando Luis Hernando; Andoni Ramirez-Garcia; Aitor Rementeria. Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications. Toxins 2019, 12, 7 .

AMA Style

Xabier Guruceaga, Uxue Perez-Cuesta, Ana Abad-Diaz De Cerio, Oskar Gonzalez, Rosa M. Alonso, Fernando Luis Hernando, Andoni Ramirez-Garcia, Aitor Rementeria. Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications. Toxins. 2019; 12 (1):7.

Chicago/Turabian Style

Xabier Guruceaga; Uxue Perez-Cuesta; Ana Abad-Diaz De Cerio; Oskar Gonzalez; Rosa M. Alonso; Fernando Luis Hernando; Andoni Ramirez-Garcia; Aitor Rementeria. 2019. "Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications." Toxins 12, no. 1: 7.

Journal article
Published: 26 November 2019 in Molecules
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Dried blood spot (DBS) has lately experienced an increase in its use in bioanalysis due to its several advantages compared with traditional blood sampling methods. Nevertheless, the use of DBS with quantitative purposes is hindered by the heterogeneous distribution of some compounds in the supporting matrix and the dependence of the response on different factors, such as the hematocrit, blood volume, and sampling position. In this study the effect of those factors in the analytical response was investigated by ultra high performance liquid chromatography coupled to fluorescence detection, using amiloride and propranolol as model compounds. The results showed a heterogeneous and drug-dependent distribution of the compounds in the blood spot. While amiloride concentration was higher in the center, propranolol concentration was higher in the periphery of the spot. Besides, the influence of the hematocrit on the quantitative results was observed. MALDI mass spectrometry imaging (MALDI-IMS) has allowed study of the distribution of the two cardiovascular drugs when they were placed in the DBS card using water:methanol solutions, demonstrating that they followed a similar distribution pattern as in blood. This work has showed the potentiality of the MALDI-IMS technique to predict the distribution of the drugs in the DBS card.

ACS Style

Beatriz Uribe; Oskar González; María Encarnación Blanco; Oihane Elena Albóniga; María Luz Alonso; Rosa María Alonso. Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS. Molecules 2019, 24, 4320 .

AMA Style

Beatriz Uribe, Oskar González, María Encarnación Blanco, Oihane Elena Albóniga, María Luz Alonso, Rosa María Alonso. Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS. Molecules. 2019; 24 (23):4320.

Chicago/Turabian Style

Beatriz Uribe; Oskar González; María Encarnación Blanco; Oihane Elena Albóniga; María Luz Alonso; Rosa María Alonso. 2019. "Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS." Molecules 24, no. 23: 4320.

Review
Published: 01 June 2019 in Bioanalysis
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The increase of fungal resistance to drugs, such as azole family, gave rise to the development of new antifungals. In this context, echinocandins emerged as a promising alternative for antifungal therapies. Following the commercialization of caspofungin in 2001, echinocandins became the first-line therapy for invasive candidiasis in different patient populations. The quantification of these drugs has gained importance since pharmacokinetic/pharmacodynamic and resistance studies are a paramount concern. This fact has led us to exhaustively examine the methodologies used for the analysis of echinocandins in biological fluids, which are mainly based on LC coupled to different detection techniques. In this review, we summarize the analytical methods for the quantification of echinocandins focusing on sample treatment, chromatographic separation and detection methods.

ACS Style

Beatriz Uribe; Oskar Gonzalez; Boubakar B Ba; Karen Gaudin; Rosa M Alonso. Chromatographic methods for echinocandin antifungal drugs determination in bioanalysis. Bioanalysis 2019, 11, 1215 -1226.

AMA Style

Beatriz Uribe, Oskar Gonzalez, Boubakar B Ba, Karen Gaudin, Rosa M Alonso. Chromatographic methods for echinocandin antifungal drugs determination in bioanalysis. Bioanalysis. 2019; 11 (12):1215-1226.

Chicago/Turabian Style

Beatriz Uribe; Oskar Gonzalez; Boubakar B Ba; Karen Gaudin; Rosa M Alonso. 2019. "Chromatographic methods for echinocandin antifungal drugs determination in bioanalysis." Bioanalysis 11, no. 12: 1215-1226.

Journal article
Published: 01 October 2017 in Journal of Pharmaceutical and Biomedical Analysis
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A novel gradient reverse phase high performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) was performed as a method for the determination of dobutamine hydrochloride (DOB) in newborn pig plasma samples. It was developed and validated after optimization of sample treatment and various chromatographic and mass spectrometric conditions. Trimethoxydobutamine (TMD) was used as internal standard. Heptafluorobutyric acid (HFBA) and ethyl acetate were used for the treatment of plasma samples. The separation of dobutamine and internal standard was done using a Kinetex F5 (50×2.1mm, 2.6μm, 100Å) analytical column. The mobile phase was a mixture of acetonitrile and HCOOH 0.01%. The column oven temperature was optimized at 40° C and the flow rate was 0.25mL/min. DOB and TMD were detected by multiple reaction monitoring (MRM) mode in ESI+, using a cone voltage (CV) of 25V and a collision energy (CE) of 25eV. The weighted calibration curve (1/x(2)) was found to be linear over the concentration range of 1-100ng/mL (r(2)>0.999). The limit of quantification (LLOQ) of the method was 1ng/mL. The values of selectivity, carryover, LLOQ, linearity, accuracy, precision, matrix effect, stability and recovery obtained meet the acceptable range according to European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines. The method was efficiently applied to quantify DOB in plasma samples from a pharmacokinetic/pharmacodynamic study in a disease model of newborn piglet.

ACS Style

O.E. Albóniga; M.L. Alonso; M.E. Blanco; Oskar Gonzalez; A. Grisaleña; M.A. Campanero; R.M. Alonso. Quantitative determination of dobutamine in newborn pig plasma samples by HPLC–MS/MS. Journal of Pharmaceutical and Biomedical Analysis 2017, 145, 178 -185.

AMA Style

O.E. Albóniga, M.L. Alonso, M.E. Blanco, Oskar Gonzalez, A. Grisaleña, M.A. Campanero, R.M. Alonso. Quantitative determination of dobutamine in newborn pig plasma samples by HPLC–MS/MS. Journal of Pharmaceutical and Biomedical Analysis. 2017; 145 ():178-185.

Chicago/Turabian Style

O.E. Albóniga; M.L. Alonso; M.E. Blanco; Oskar Gonzalez; A. Grisaleña; M.A. Campanero; R.M. Alonso. 2017. "Quantitative determination of dobutamine in newborn pig plasma samples by HPLC–MS/MS." Journal of Pharmaceutical and Biomedical Analysis 145, no. : 178-185.

Article
Published: 14 June 2017 in ELECTROPHORESIS
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A pilot study for the investigation of the maturation grade of children has been carried out using plasma samples already analyzed in a previous pharmacokinetic study. By using a meticulous data treatment, possible confounding factors that may hinder the obtained results were identified. By doing so, it was possible to obtain enough evidence to support the feasibility of performing a larger study eluding some unwanted variability and minimizing not only the number of subjects involved but also the time and money spent on the study. In the pilot study the metabolic profiles obtained using UHPLC-TOF-MS technique of plasma samples from 14 newborn piglets (<5 days) were compared with the plasma profiles of 16 infant piglets (8 weeks). The type of anaesthesia administered, gender, vein or artery of blood extraction and time of sampling were studied as possible confounding factors. Unsupervised analysis by principal component analysis (PCA) clearly differentiated between neonates and children. During the data treatment and the statistical analysis, the effect of confounding factors such as the anaesthetic regimen was identified and removed, while the effect of the rest of studied factors was not considered relevant, and the discrimination between the two groups based on the age was maintained. This allowed extracting relevant conclusions for a future study design while avoiding the unnecessary sacrifice of animals. Furthermore, the results obtained demonstrate the utility of metabolomics in the discovery of novel putative plasma biomarkers such as carnitines that can be correlated with the maturation state of paediatric patients.

ACS Style

María Encarnación Blanco; Oskar González; Oihane Elena Albóniga; María Luz Alonso; Rosa María Alonso. Metabolomic analysis for the study of maturation in pediatrics: Effect of confounding factors in a pilot study. ELECTROPHORESIS 2017, 38, 2323 -2330.

AMA Style

María Encarnación Blanco, Oskar González, Oihane Elena Albóniga, María Luz Alonso, Rosa María Alonso. Metabolomic analysis for the study of maturation in pediatrics: Effect of confounding factors in a pilot study. ELECTROPHORESIS. 2017; 38 (18):2323-2330.

Chicago/Turabian Style

María Encarnación Blanco; Oskar González; Oihane Elena Albóniga; María Luz Alonso; Rosa María Alonso. 2017. "Metabolomic analysis for the study of maturation in pediatrics: Effect of confounding factors in a pilot study." ELECTROPHORESIS 38, no. 18: 2323-2330.

Original
Published: 04 March 2017 in Chromatographia
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This work reports the development and validation of an ultra-high-performance liquid chromatography method to separate 11 different cardiovascular drugs: acenocoumarol, amiloride, bisoprolol, fluvastatin, furosemide, glibenclamide, hydrochlorothiazide, rosiglitazone (internal standard), valsartan, verapamil and warfarin. Detection of the analytes was carried out by means of photodiode array and fluorescence detection. Initially, the most significant variables in liquid chromatography (pH of the mobile phase, nature of the organic modifier and stationary phase type) were studied simultaneously in a systematic way. Taking into account the resolution obtained for the different chromatographic separations, pH 4.5, methanol and C18 were chosen as mobile phase pH, organic modifier and stationary phase, respectively. The method was validated and applied to the analysis of real human plasma samples using a solid phase extraction sample treatment, and the robustness of the chromatographic separation was studied by experimental design. The reported method allows the separation of all the analytes and the IS in less than 6 min, and, furthermore, it simplifies the analysis of drugs used in combined cardiovascular therapy by applying a fast and simple methodology.

ACS Style

Oskar González Mendia; María Encarnación Blanco; Estitxu Rico; María Luz Alonso; Miren Itxaso Maguregui; Rosa María Alonso. Efficient Method Development and Validation for the Determination of Cardiovascular Drugs in Human Plasma by SPE–UHPLC–PDA–FLD. Chromatographia 2017, 80, 605 -615.

AMA Style

Oskar González Mendia, María Encarnación Blanco, Estitxu Rico, María Luz Alonso, Miren Itxaso Maguregui, Rosa María Alonso. Efficient Method Development and Validation for the Determination of Cardiovascular Drugs in Human Plasma by SPE–UHPLC–PDA–FLD. Chromatographia. 2017; 80 (4):605-615.

Chicago/Turabian Style

Oskar González Mendia; María Encarnación Blanco; Estitxu Rico; María Luz Alonso; Miren Itxaso Maguregui; Rosa María Alonso. 2017. "Efficient Method Development and Validation for the Determination of Cardiovascular Drugs in Human Plasma by SPE–UHPLC–PDA–FLD." Chromatographia 80, no. 4: 605-615.

Journal article
Published: 01 December 2016 in Zebrafish
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Zebrafish larvae (Danio rerio) are increasingly used to translate findings regarding drug efficacy and safety from in vitro-based assays to vertebrate species, including humans. However, the limited understanding of drug exposure in this species hampers its implementation in translational research. Using paracetamol as a paradigm compound, we present a novel method to characterize pharmacokinetic processes in zebrafish larvae, by combining sensitive bioanalytical methods and nonlinear mixed effects modeling. The developed method allowed quantification of paracetamol and its two major metabolites, paracetamol-sulfate and paracetamol-glucuronide in pooled samples of five lysed zebrafish larvae of 3 days post-fertilization. Paracetamol drug uptake was quantified to be 0.289 pmole/min and paracetamol clearance was quantified to be 1.7% of the total value of the larvae. With an average volume determined to be 0.290 μL, this yields an absolute clearance of 2.96 × 107 L/h, which scales reasonably well with clearance rates in higher vertebrates. The developed methodology will improve the success rate of drug screens in zebrafish larvae and the translation potential of findings, by allowing the establishment of accurate exposure profiles and thereby also the establishment of concentration–effect relationships.

ACS Style

Vasudev Kantae; Elke H.J. Krekels; Anita Ordas; Oskar Gonzalez; Rob Christiaan van Wijk; Amy C. Harms; Peter I. Racz; Piet H. Van Der Graaf; Herman Spaink; Thomas Hankemeier. Pharmacokinetic Modeling of Paracetamol Uptake and Clearance in Zebrafish Larvae: Expanding the Allometric Scale in Vertebrates with Five Orders of Magnitude. Zebrafish 2016, 13, 504 -510.

AMA Style

Vasudev Kantae, Elke H.J. Krekels, Anita Ordas, Oskar Gonzalez, Rob Christiaan van Wijk, Amy C. Harms, Peter I. Racz, Piet H. Van Der Graaf, Herman Spaink, Thomas Hankemeier. Pharmacokinetic Modeling of Paracetamol Uptake and Clearance in Zebrafish Larvae: Expanding the Allometric Scale in Vertebrates with Five Orders of Magnitude. Zebrafish. 2016; 13 (6):504-510.

Chicago/Turabian Style

Vasudev Kantae; Elke H.J. Krekels; Anita Ordas; Oskar Gonzalez; Rob Christiaan van Wijk; Amy C. Harms; Peter I. Racz; Piet H. Van Der Graaf; Herman Spaink; Thomas Hankemeier. 2016. "Pharmacokinetic Modeling of Paracetamol Uptake and Clearance in Zebrafish Larvae: Expanding the Allometric Scale in Vertebrates with Five Orders of Magnitude." Zebrafish 13, no. 6: 504-510.

Journal article
Published: 27 October 2016 in EKAIA Euskal Herriko Unibertsitateko Zientzia eta Teknologia Aldizkaria
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Lan honetan Odol Tanta Lehorraren (OTLa) laginketa-teknikaren fidagarritasuna ikertu da farmakoen analisirako fotodiodo- eta fluoreszentzia-detektagailuei akoplatutako bereizmen oso altuko likido-kromatografiaren (UHPLC-PDA-FLD) bidez. OTLak, odol-tanta bat kotoi-paperezko euskarri batean jartzean eta lehortzen uztean datzan teknikak, azken urteotan erabileraren handipen garrantzitsua antzeman du bioanalisian. OTLak ohiko odol-analisiekiko hainbat abantaila erakutsi arren, analisi kuantitatiboaren ikuspuntutik hainbat faktorerekiko mendekotasuna duela antzeman da. Ikerketa honetan faktore batzuek (hematokritoa, odol-bolumena eta laginketa-puntua) farmakoen determinazioan duten eragina aztertu da, horretarako amilorida, propranolola eta valsartan farmakoak eredu gisa erabiliz. Emaitzetan oinarrituta, zuloaren kokapenak eta hematokritoak analisien zehaztasunean eta doitasunean eragina dutela ondorioztatu da, teknika honen aplikazio kuantitatiboa mugatuz. Bestalde, analitoen sakabanaketa odol-tantan zehar analitoen propietate fisiko-kimikoen mendekoa dela ikusi da, metodo analitikoaren garapenean analito bakoitzaren sakabanaketa aztertu behar dela ondorioztatuz.

ACS Style

Beatriz Uribe; Oskar Gonzalez; Rosa M. Alonso; Rosa M. Alonso Rojas. Odol Tanta Lehorraren fidagarritasunaren azterketa farmakoen analisi kuantitatiborako UHPLC-PDA-FLDren bidez. EKAIA Euskal Herriko Unibertsitateko Zientzia eta Teknologia Aldizkaria 2016, 19 -36.

AMA Style

Beatriz Uribe, Oskar Gonzalez, Rosa M. Alonso, Rosa M. Alonso Rojas. Odol Tanta Lehorraren fidagarritasunaren azterketa farmakoen analisi kuantitatiborako UHPLC-PDA-FLDren bidez. EKAIA Euskal Herriko Unibertsitateko Zientzia eta Teknologia Aldizkaria. 2016; (30):19-36.

Chicago/Turabian Style

Beatriz Uribe; Oskar Gonzalez; Rosa M. Alonso; Rosa M. Alonso Rojas. 2016. "Odol Tanta Lehorraren fidagarritasunaren azterketa farmakoen analisi kuantitatiborako UHPLC-PDA-FLDren bidez." EKAIA Euskal Herriko Unibertsitateko Zientzia eta Teknologia Aldizkaria , no. 30: 19-36.

Conference paper
Published: 04 December 2015 in Proceedings of MOL2NET, International Conference on Multidisciplinary Sciences
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In this work, the reliability of Dried Blood Spot (DBS) as a sampling technique for drug analysis was studied by Ultra High Performance Liquid Chromatography coupled to Photodiode-Array and Fluorescence Detection (UHPLC-PDA-FLUO). DBS microsampling, a technique based on placing a drop of blood in a cotton support that is allowed to air dry, has lately noticed an increase in use in bioanalysis. Even thought it offers several advantages compared to common blood sampling methods, it also shows some limitations for quantitative analysis due to the dependence on different factors. In this study, the influence of some of them (haematocrit, blood volume and sampling position) has been investigated, using amiloride, propranolol and valsartan drugs as model compounds. According to the results, it has been concluded that the sampling position and the haematocrit have influence in the accuracy and precision of the quantitative results, therefore limiting the use of this technique. On the other hand, dispersion of the analytes in the blood drop depends on their physicochemical properties which implies that the distribution of each analyte must be carefully studied during method development.

ACS Style

Oskar Gonzalez; Rosa Alonso; Beatriz Uribe; Oihane Alboniga. Study of Dried Blood Spot reliability for quantitative drug analysis by UHPLC-PDA-FLUO. Proceedings of MOL2NET, International Conference on Multidisciplinary Sciences 2015, 1 .

AMA Style

Oskar Gonzalez, Rosa Alonso, Beatriz Uribe, Oihane Alboniga. Study of Dried Blood Spot reliability for quantitative drug analysis by UHPLC-PDA-FLUO. Proceedings of MOL2NET, International Conference on Multidisciplinary Sciences. 2015; ():1.

Chicago/Turabian Style

Oskar Gonzalez; Rosa Alonso; Beatriz Uribe; Oihane Alboniga. 2015. "Study of Dried Blood Spot reliability for quantitative drug analysis by UHPLC-PDA-FLUO." Proceedings of MOL2NET, International Conference on Multidisciplinary Sciences , no. : 1.

Journal article
Published: 01 September 2015 in Bioanalysis
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The great impact of cardiovascular diseases in human health has led to the development of a huge number of drugs and therapies to improve the treatment of these diseases. Cardiovascular drug analysis in biological fluids constitutes an important challenge for analytical scientists. There is a clear need for reliable methods to carry out both qualitative and quantitative analysis in a short time of analysis. Different problems such as drug monitoring, analysis of metabolites, study of drugs interactions, drugs residues or degradation products, chiral separation, and screening and confirmation of drugs of abuse in doping control must be solved. New trends in sample preparation, instrumental and column technology advances in LC and innovations in MS are described in this work.

ACS Style

Oskar González; Nerea Ferreirós; María Encarnación Blanco; Rosa M Alonso. Cardiovascular drug determination in bioanalysis: an update. Bioanalysis 2015, 7, 2399 -2417.

AMA Style

Oskar González, Nerea Ferreirós, María Encarnación Blanco, Rosa M Alonso. Cardiovascular drug determination in bioanalysis: an update. Bioanalysis. 2015; 7 (18):2399-2417.

Chicago/Turabian Style

Oskar González; Nerea Ferreirós; María Encarnación Blanco; Rosa M Alonso. 2015. "Cardiovascular drug determination in bioanalysis: an update." Bioanalysis 7, no. 18: 2399-2417.

Journal article
Published: 22 May 2015 in Analytical Chemistry
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The possible presence of matrix effect is one of the main concerns in liquid chromatography-mass spectrometry (LC-MS)-driven bioanalysis due to its impact on the reliability of the obtained quantitative results. Here we propose an approach to correct for the matrix effect in LC-MS with electrospray ionization using postcolumn infusion of eight internal standards (PCI-IS). We applied this approach to a generic ultraperformance liquid chromatography-time-of-flight (UHPLC-TOF) platform developed for small-molecule profiling with a main focus on drugs. Different urine samples were spiked with 19 drugs with different physicochemical properties and analyzed in order to study matrix effect (in absolute and relative terms). Furthermore, calibration curves for each analyte were constructed and quality control samples at different concentration levels were analyzed to check the applicability of this approach in quantitative analysis. The matrix effect profiles of the PCI-ISs were different: this confirms that the matrix effect is compound-dependent, and therefore the most suitable PCI-IS has to be chosen for each analyte. Chromatograms were reconstructed using analyte and PCI-IS responses, which were used to develop an optimized method which compensates for variation in ionization efficiency. The approach presented here improved the results in terms of matrix effect dramatically. Furthermore, calibration curves of higher quality are obtained, dynamic range is enhanced, and accuracy and precision of QC samples is increased. The use of PCI-ISs is a very promising step toward an analytical platform free of matrix effect, which can make LC-MS analysis even more successful, adding a higher reliability in quantification to its intrinsic high sensitivity and selectivity.

ACS Style

Oskar Gonzalez; Michael Van Vliet; Carola W. N. Damen; Frans M. Van Der Kloet; Rob Vreeken; Thomas Hankemeier. Matrix Effect Compensation in Small-Molecule Profiling for an LC–TOF Platform Using Multicomponent Postcolumn Infusion. Analytical Chemistry 2015, 87, 5921 -5929.

AMA Style

Oskar Gonzalez, Michael Van Vliet, Carola W. N. Damen, Frans M. Van Der Kloet, Rob Vreeken, Thomas Hankemeier. Matrix Effect Compensation in Small-Molecule Profiling for an LC–TOF Platform Using Multicomponent Postcolumn Infusion. Analytical Chemistry. 2015; 87 (12):5921-5929.

Chicago/Turabian Style

Oskar Gonzalez; Michael Van Vliet; Carola W. N. Damen; Frans M. Van Der Kloet; Rob Vreeken; Thomas Hankemeier. 2015. "Matrix Effect Compensation in Small-Molecule Profiling for an LC–TOF Platform Using Multicomponent Postcolumn Infusion." Analytical Chemistry 87, no. 12: 5921-5929.

Validation study
Published: 09 March 2015 in Drug Testing and Analysis
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In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h). Copyright © 2015 John Wiley & Sons, Ltd.

ACS Style

M.E. Blanco; E. Encinas; Oskar Gonzalez; E. Rico; V. Vozmediano; Elena Suarez; R.M. Alonso. Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS. Drug Testing and Analysis 2015, 7, 804 -811.

AMA Style

M.E. Blanco, E. Encinas, Oskar Gonzalez, E. Rico, V. Vozmediano, Elena Suarez, R.M. Alonso. Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS. Drug Testing and Analysis. 2015; 7 (9):804-811.

Chicago/Turabian Style

M.E. Blanco; E. Encinas; Oskar Gonzalez; E. Rico; V. Vozmediano; Elena Suarez; R.M. Alonso. 2015. "Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS." Drug Testing and Analysis 7, no. 9: 804-811.

Journal article
Published: 12 October 2014 in Analytical and Bioanalytical Chemistry
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Eight human plasma preparation protocols were evaluated for their suitability for metabolomic studies by ultra-high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry: organic solvent protein precipitation (PPT) with either methanol or acetonitrile in 2:1 and 3:1 (v/v) ratios with plasma; solid-phase extraction (SPE) using C18 or HybridSPE cartridges; and a combination of PPT and SPE C18 cartridges and microextraction by packed sorbent. A study design in which the order of injection of the samples was not randomized is presented. The analyses were conducted in a BEH C18 column (1.7 μm, 2.1 mm × 100 mm) using a linear gradient from 100 % water to 100 % methanol, both with 0.1 % formic acid, in 21 min. The most reproducible protocol considering both the univariate and the multivariate analysis results was PPT with acetonitrile in a 2:1 (v/v) ratio with plasma, offering a mean coefficient of variation of the area of all the detected features of 0.15 and one of the best clusterings in the principal component analysis plots. On the other hand, the highest number of extracted features was achieved using methanol in a 2:1 (v/v) ratio with plasma as the PPT solvent, closely followed by the same protocol with acetonitrile in a 2:1 (v/v) ratio with plasma, which offered only 1.2 % fewer repeatable features. In terms of concentration of remaining protein, protocols based on PPT with acetonitrile provided cleaner extracts than protocols based on PPT with methanol. Finally, pairwise comparison showed that the use of PPT- and SPE-based protocols offers a different coverage of the metabolome. Graphical Abstract

ACS Style

Estitxu Rico; Oskar Gonzalez; María Encarnación Blanco; Rosa María Alonso. Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS. Analytical and Bioanalytical Chemistry 2014, 406, 7641 -7652.

AMA Style

Estitxu Rico, Oskar Gonzalez, María Encarnación Blanco, Rosa María Alonso. Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS. Analytical and Bioanalytical Chemistry. 2014; 406 (29):7641-7652.

Chicago/Turabian Style

Estitxu Rico; Oskar Gonzalez; María Encarnación Blanco; Rosa María Alonso. 2014. "Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS." Analytical and Bioanalytical Chemistry 406, no. 29: 7641-7652.

Review
Published: 01 August 2014 in Journal of Chromatography A
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Method validation is a mandatory step in bioanalysis, to evaluate the ability of developed methods in providing reliable results for their routine application. Even if some organisations have developed guidelines to define the different parameters to be included in method validation (FDA, EMA); there are still some ambiguous concepts in validation criteria and methodology that need to be clarified. The methodology to calculate fundamental parameters such as the limit of quantification has been defined in several ways without reaching a harmonised definition, which can lead to very different values depending on the applied criterion. Other parameters such as robustness or ruggedness are usually omitted and when defined there is not an established approach to evaluate them. Especially significant is the case of the matrix effect evaluation which is one of the most critical points to be studied in LC-MS methods but has been traditionally overlooked. Due to the increasing importance of bioanalysis this scenario is no longer acceptable and harmonised criteria involving all the concerned parties should be arisen. The objective of this review is thus to discuss and highlight several essential aspects of method validation, focused in bioanalysis. The overall validation process including common validation parameters (selectivity, linearity range, precision, accuracy, stability…) will be reviewed. Furthermore, the most controversial parameters (limit of quantification, robustness and matrix effect) will be carefully studied and the definitions and methodology proposed by the different regulatory bodies will be compared. This review aims to clarify the methodology to be followed in bioanalytical method validation, facilitating this time consuming step.

ACS Style

Oskar Gonzalez; María Encarnación Blanco; Gorka Iriarte; Luis Bartolomé; Miren Itxaso Maguregui; Rosa M. Alonso. Bioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effect. Journal of Chromatography A 2014, 1353, 10 -27.

AMA Style

Oskar Gonzalez, María Encarnación Blanco, Gorka Iriarte, Luis Bartolomé, Miren Itxaso Maguregui, Rosa M. Alonso. Bioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effect. Journal of Chromatography A. 2014; 1353 ():10-27.

Chicago/Turabian Style

Oskar Gonzalez; María Encarnación Blanco; Gorka Iriarte; Luis Bartolomé; Miren Itxaso Maguregui; Rosa M. Alonso. 2014. "Bioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effect." Journal of Chromatography A 1353, no. : 10-27.

Journal article
Published: 01 February 2011 in Journal of Chromatography B
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This paper reports an LC–MS/MS method with positive electrospray ionization for the screening of commonly prescribed cardiovascular drugs in human plasma, including compounds with antihypertensive (57), antidiabetic (12), hypolipemiant (5), anticoagulant (2) and platelet anti-aggregation (2) effects. Sample treatment consisted of a simple protein precipitation with MeOH/0.1 M ZnSO4 (4:1, v/v) solution after the addition of internal standard, followed by evaporation and reconstitution. Analytes separation was performed on a Polar-RP column (150 mm × 2 mm, 4 μm) using a gradient elution of 15 min. The MS system was operated in MRM mode, monitoring one quantitation and one confirmation transition for each analyte. The recovery of the protein precipitation step ranged from 50 to 70% for most of the compounds, while some were considerably affected by matrix effects. Since several analytes fulfilled the linearity, accuracy and precision values required by the ICH guidelines, the method proved to be suitable for their quantitative analysis. The limits of quantitation varied from 0.38 to 9.1 μg/L and the limits of detection from 0.12 to 5.34 μg/L. The method showed to be suitable for the detection of plasma samples of patients under cardiovascular treatment with the studied drugs, and for 55 compounds reliable quantitative results could be obtained.

ACS Style

Oskar Gonzalez; Rosa Maria Alonso; Nerea Ferreirós; Wolfgang Weinmann; Ralf Zimmermann; Sebastian Dresen. Development of an LC–MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy. Journal of Chromatography B 2011, 879, 243 -252.

AMA Style

Oskar Gonzalez, Rosa Maria Alonso, Nerea Ferreirós, Wolfgang Weinmann, Ralf Zimmermann, Sebastian Dresen. Development of an LC–MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy. Journal of Chromatography B. 2011; 879 (3-4):243-252.

Chicago/Turabian Style

Oskar Gonzalez; Rosa Maria Alonso; Nerea Ferreirós; Wolfgang Weinmann; Ralf Zimmermann; Sebastian Dresen. 2011. "Development of an LC–MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy." Journal of Chromatography B 879, no. 3-4: 243-252.