Publications by authors named "Rosa Maria Alonso"

18 Publications

  • Page 1 of 1

Optimization and Validation of HS-GC/MS Method for the Controlled Release Study of Microencapsulated Specific Bioattractants for Target-Plaguicide Production.

Molecules 2021 Feb 13;26(4). Epub 2021 Feb 13.

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

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 , 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.
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http://dx.doi.org/10.3390/molecules26040996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917701PMC
February 2021

Grape polyphenols supplementation for exercise-induced oxidative stress.

J Int Soc Sports Nutr 2021 Jan 7;18(1). Epub 2021 Jan 7.

Analytical Chemistry Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain.

Exercise induces free radicals' overproduction and therefore, an enhancement of oxidative stress, defined as an imbalance between the production of reactive species and the intrinsic antioxidant defense. Redox activity of reactive species plays an important and a positive role on exercise adaptation, but these species at very high concentrations have detrimental effects. As a result, the use of antioxidant supplements for reducing oxidative stress can be an effective health strategy to maintain an optimal antioxidant status. In this sense, grapes are an important source of natural antioxidants due to their high content in polyphenols. They have shown antioxidant potential benefits for the reduction of intense exercise effect in athletes of different sport disciplines. Consequently, it is plausible to hypothesize that a strategic supplementation with grape based products may be a good approach to mitigate the exercise induced oxidative stress. The goal of this review is to present the state of the art of supplementation effects with grape beverages and grape extracts on the oxidative stress markers in athletes. The data of polyphenolic dosages, participant characteristics and exercise protocols are reported.
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http://dx.doi.org/10.1186/s12970-020-00395-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789302PMC
January 2021

Analysis of the Heterogeneous Distribution of Amiloride and Propranolol in Dried Blood Spot by UHPLC-FLD and MALDI-IMS.

Molecules 2019 Nov 26;24(23). Epub 2019 Nov 26.

Analytical Chemistry Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Sarriena s/n, 48940 Leioa, Biscay, Basque Country, Spain.

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.
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http://dx.doi.org/10.3390/molecules24234320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930677PMC
November 2019

Formulation of Carbopol/Poly(2-ethyl-2-oxazoline)s Mucoadhesive Tablets for Buccal Delivery of Hydrocortisone.

Polymers (Basel) 2018 Feb 11;10(2). Epub 2018 Feb 11.

School of Pharmacy, University of Reading, Whiteknights, P.O. Box 224, Reading RG6 6AD, UK.

Poly(2-ethyl-2-oxazoline) has become an excellent alternative to the use of poly(ethylene glycol) in pharmaceutical formulations due to its valuable physicochemical and biological properties. This work presents a formulation of poorly-water soluble drug, hydrocortisone, using interpolymer complexes and physical blends of poly(2-ethyl-2-oxazoline)s and two Carbopols (Carbopol 974 and Carbopol 971) for oromucosal administration. The swelling, hydrocortisone release and mucoadhesive properties of a series of tablet formulations obtained by combination of different Carbopols with poly(2-ethyl-2-oxazoline)s of different molecular weights have been evaluated in vitro.
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http://dx.doi.org/10.3390/polym10020175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415335PMC
February 2018

Metabolomic analysis for the study of maturation in pediatrics: Effect of confounding factors in a pilot study.

Electrophoresis 2017 09 14;38(18):2323-2330. Epub 2017 Jun 14.

Analytical Chemistry Department, Science and Technology Faculty, University of the Basque Country (UPV/EHU), Bilbao, Basque Country, Spain.

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.
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http://dx.doi.org/10.1002/elps.201700026DOI Listing
September 2017

Evaluation of human plasma sample preparation protocols for untargeted metabolic profiles analyzed by UHPLC-ESI-TOF-MS.

Anal Bioanal Chem 2014 Nov 12;406(29):7641-52. Epub 2014 Oct 12.

Analytical Chemistry Department, Faculty of Science and Technology, University of Basque Country/EHU, P.O. Box 644, 48080, Bilbao, Spain,

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.
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http://dx.doi.org/10.1007/s00216-014-8212-yDOI Listing
November 2014

Development of an LC-MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy.

J Chromatogr B Analyt Technol Biomed Life Sci 2011 Feb 15;879(3-4):243-52. Epub 2010 Dec 15.

Analytical Chemistry Department, Science and Technology Faculty Leioa, Spain.

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 m x 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.
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http://dx.doi.org/10.1016/j.jchromb.2010.12.007DOI Listing
February 2011

LC-MS/MS method for the determination of several drugs used in combined cardiovascular therapy in human plasma.

J Chromatogr B Analyt Technol Biomed Life Sci 2010 Oct 6;878(28):2685-92. Epub 2010 Aug 6.

Analytical Chemistry Department, Science and Technology Faculty, Basque Country University/EHU, P.O. Box 644, 48080 Bilbao, Basque Country, Spain.

A simple, fast and validated method is reported for the simultaneous analysis, in human plasma, of several drugs usually combined in cardiovascular therapy (atenolol, bisoprolol, hydrochlorothiazide, chlorthalidone, salicylic acid, enalapril and its active metabolite enalaprilat, valsartan and fluvastatin) using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI), working in multiple reaction monitoring mode (MRM). Separation of analytes and internal standard (pravastatin) was performed on a Luna C18(2) (150mm×4.6mm, 3μm) column using a gradient elution mode with a run time of 15min. The mobile phase consisted of a mixture of acetonitrile and water containing 0.01% formic acid and 10mM ammonium formate at pH 4.1. Sample treatment consisted of a simple protein precipitation with acetonitrile, enabling a fast analysis. The method showed good linearity, precision (RSD% values between 0.7% and 12.7%) and accuracy (relative error values between 0.9% and 14.0%). Recoveries were within 68-106% range and the ion-suppression was not higher than 22% for any analyte. The method was successfully applied to plasma samples obtained from patients under combined cardiovascular treatment.
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http://dx.doi.org/10.1016/j.jchromb.2010.07.026DOI Listing
October 2010

Validation of a fast liquid chromatography-UV method for the analysis of drugs used in combined cardiovascular therapy in human plasma.

J Chromatogr B Analyt Technol Biomed Life Sci 2009 Oct 19;877(27):3045-53. Epub 2009 Jul 19.

Pintura Saila, Arte Ederretako Fakultatea, Euskal Herriko Unibertsitatea/UPV, P.K. 644, 48080 Bilbo, Basque Country, Spain.

Ultra-performance liquid chromatography (UPLC) was investigated as a faster alternative to high-performance liquid chromatography (HPLC) for the simultaneous analysis of drugs usually prescribed in cardiovascular therapy. Upon a previously developed and validated solid phase extraction (SPE)-HPLC-photodiode array (PDA)-fluorescence (FLR) method, separation of chlorthalidone (CLTD; diuretic), valsartan and its metabolite (VAL and VAL-M1 respectively; angiotensin II receptor antagonist drugs) and fluvastatin (FLUV; statin) was performed in human plasma using an RP C18 column (50mmx2.1mm, 1.7microm, Waters Acquity UPLC (BEH)) and a tunable UV-vis (TUV) detector. After method transfer, different system variables were modulated to study the evolution of responses of the analytes and the endogenous interferences. The improved method was fully validated and the results were compared with its precursor HPLC method relating to analysis time, efficiency and sensitivity. The studied compounds were separated in less than 8min and the method showed good linearity (20-3000microg/L for chlorthalidone, 110-1100microg/L for valsartan-M1, 67-1900microg/L for valsartan and 48-1100microg/L for fluvastatin), precision and accuracy. The proposed method was found to be reproducible (RSD<10%), accurate (RE<15%), robust and suitable for quantitative analysis of the studied drugs in plasma obtained from patients under combined cardiovascular treatment.
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http://dx.doi.org/10.1016/j.jchromb.2009.07.018DOI Listing
October 2009

Optimization and validation of a SPE-HPLC-PDA-fluorescence method for the simultaneous determination of drugs used in combined cardiovascular therapy in human plasma.

J Pharm Biomed Anal 2009 Nov 5;50(4):630-9. Epub 2008 Nov 5.

Kimika Analitikoa Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea/UPV, P.K. 644, 48080 Bilbo, Basque Country, Spain.

This paper reports the chemometrical optimization and the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-Fluo) method for the simultaneous analysis, in human plasma, of drugs usually combined in cardiovascular therapy. Separation of chlorthalidone (CLTD), valsartan (VAL), valsartan-M1 (VAL-M1), fluvastatin (FLUV) and the internal standard (IS) candesartan cilexetil was performed on a dC18 Atlantis column (100 mm x 3.9 mm, 3 microm) using a gradient with a run time of 15 min. The mobile phase consisted of a mixture of acetonitrile and water containing 0.01% of formic acid and 10 mM of ammonium formate at pH 4.1. UV and fluorimetric (valsartan, its metabolite and fluvastatin) detectors were used. The sample preparation consisted of protein precipitation using acetonitrile suited to a solid-phase extraction (SPE) on a Strata-X cartridge for sample clean-up. Method validation was developed following the recommendations for bioanalytical method validation of International Conference on Harmonisation (ICH) and Food and Drug Administration (FDA) organizations. The method showed good linearity (31-3000 microg/l for chlorthalidone, 20-1000 microg/l for valsartan-M1, 10-5000 microg/l for valsartan and 14-1000 microg/l for fluvastatin), precision and accuracy. Recoveries were in the range of 78-91%. This method allowed the determination of these drugs in human plasma samples obtained from patients under cardiovascular treatment.
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http://dx.doi.org/10.1016/j.jpba.2008.10.037DOI Listing
November 2009

Separation and quantitation of several angiotensin II receptor antagonist drugs in human urine by a SPE-HPLC-DAD method.

J Sep Sci 2008 Mar;31(4):667-76

Departamento de Química Analítica, Facultad de Ciencia y Tecnología, Leioa, Spain.

In this work, an SPE-HPLC method coupled to photodiode array detection was validated in human urine matrix, in order to monitor four antihypertensive angiotensin II receptor antagonist drugs in patients under cardiovascular treatment. For that purpose, experimental design was used. Quantitation was accomplished by the internal standard method. The obtained LOQs were 95, 113, 125, and 85 ng/mL for eprosartan, telmisartan, irbesartan, and valsartan, respectively. The intraday and interday precision and accuracy at four concentration levels in the working range (LOQ-15 microg/mL) were always lower than 11% RSD and 8% relative error. The urine samples proved to be stable during 4 h at room temperature, after three thaw-freeze cycles, and for 2 months at -20 degrees C. No interferences from other endogenous compounds or co-administered drugs were found. The method has been successfully applied to monitor the renal elimination of eprosartan and valsartan during 24 h.
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http://dx.doi.org/10.1002/jssc.200700442DOI Listing
March 2008

Validated quantitation of angiotensin II receptor antagonists (ARA-II) in human plasma by liquid-chromatography-tandem mass spectrometry using minimum sample clean-up and investigation of ion suppression.

Ther Drug Monit 2007 Dec;29(6):824-34

Institute of Forensic Medicine, Forensic Toxicology, University Hospital, Freiburg, Germany.

For the quantitation of angiotensin II receptor antagonists (ARA-II) in human plasma, a method using liquid-chromatography (LC)-electrospray ionization tandem mass spectrometry (MS/MS) has been developed with respect to simple sample clean-up and investigation of ion suppression effects. For sample preparation, protein precipitation using zinc sulphate and methanol showed advantages in speed, recovery, and reproducibility over solid-phase extraction. A triple quadrupole mass spectrometer (Sciex API 365) with turbo ionspray source was used for detection of compounds with multireaction monitoring (MRM) of two transitions per compound. Suppression effects caused by endogenous matrix compounds were investigated by post-column infusion of analytes and LC analysis of precipitates of blank plasma samples and could be excluded. A validation was performed for the ARA-II drugs (valsartan, irbesartan, losartan and its active metabolite EXP 3174, eprosartan, candesartan, and telmisartan). The developed method showed good intra- and interday precision (<12% relative standard deviation) and accuracy (<11.5% bias) at different concentrations for all the studied compounds. The calculated lower limits of quantitation were between 7 and 13 ng/mL, and the compounds were stable during the analytical process. These rather expensive drugs against hypertension are prescribed with increasing numbers in Europe and the industrialized nations. Complications might arise from overdosage or metabolic disorders. However, drug monitoring is not usually performed. Because the therapeutic concentrations range from a few nanograms to hundreds of nanograms per milliliter for the different drugs, and they are not amenable to gas chromatography/MS analysis because of their high molecular weight and polarity, the LC-MS/MS method is the golden standard for therapeutic drug monitoring and for clinical and forensic toxicology of ARA-II drugs.
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http://dx.doi.org/10.1097/FTD.0b013e31815d0f66DOI Listing
December 2007

Biovalidation of an SPE-HPLC-UV-fluorescence method for the determination of valsartan and its metabolite valeryl-4-hydroxy-valsartan in human plasma.

J Sep Sci 2007 Sep;30(14):2231-40

Kimika Analitikoaren Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea/UPV, Bilbo, Basque Country, Spain.

A simple and fast method for the simultaneous determination of the antihypertensive drug Valsartan and its metabolite in human plasma has been validated. The proposed method deals with SPE, followed by an HPLC separation coupled with fluorimetric and photometric detection. The optimization of the SPE-HPLC method was achieved by an experimental design. The separation was performed on an RP C18 Atlantis 100 mmx3.9 mm column. The mobile phase consisted of a mixture of ACN 0.025% TFA and phosphate buffer (5 mM, pH = 2.5) 0.025% TFA and was delivered in gradient mode at a flow rate of 1.30 mL/min. The eluent was monitored with a fluorescence detector at 234 and 378 nm excitation and emission wavelengths, respectively, and at 254 nm using a photometric detector. The full analytical validation was performed according to the Food and Drug Administration (FDA) 'guidance for industry: bioanalytical method validation' and the recoveries obtained for Valsartan and its metabolite ranged from 94.6 to 108.8%. The validated method was successfully applied to 12 plasma samples obtained from patients under antihypertensive treatment with Valsartan.
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http://dx.doi.org/10.1002/jssc.200700033DOI Listing
September 2007

[Occupational exposure to airborne fungi and bacteria in a household recycled container sorting plant ].

Rev Iberoam Micol 2007 Jun;24(2):131-5

Centro Nacional de Condiciones de Trabajo, Instituto Nacional de Seguridad e Higiene en el Trabajo, C/Dulcet 2-10, 08034 Barcelona, Spain.

Several studies have showed an association between the work in waste treatment plants and occupational health problems such as irritation of skin, eyes and mucous membranes, pulmonary diseases, gastrointestinal problems and symptoms of organic dust toxic syndrome (ODTS). These symptoms have been related to bioaerosol exposure. The aim of this study was to investigate the occupational exposure to biological agents in a plant sorting source-separated packages (plastics materials, ferric and non-ferric metals) household waste. Airborne samples were collected with M Air T Millipore sampler. The concentration of total fungi and bacteria and gram-negative bacteria were determined and the most abundant genera were identified. The results shown that the predominant airborne microorganisms were fungi, with counts greater than 12,000 cfu/m(3) and gram-negative bacteria, with a environmental concentration between 1,395 and 5,280 cfu/m(3). In both cases, these concentrations were higher than levels obtained outside of the sorting plant. Among the fungi, the predominant genera were Penicillium and Cladosporium, whereas the predominant genera of gram-negative bacteria were Escherichia, Enterobacter, Klebsiella and Serratia. The present study shows that the workers at sorting source-separated packages (plastics materials, ferric and non-ferric metals) domestic waste plant may be exposed to airborne biological agents, especially fungi and gram-negative bacteria.
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http://dx.doi.org/10.1016/s1130-1406(07)70028-1DOI Listing
June 2007

Hydrolysis and transesterification reactions of candesartan cilexetil observed during the solid phase extraction procedure.

J Chromatogr B Analyt Technol Biomed Life Sci 2007 Aug 13;855(2):134-8. Epub 2007 Apr 13.

Institute of Forensic Medicine, Forensic Toxicology, University Hospital, Albertstrasse 9, Freiburg, Germany.

Candesartan cilexetil is an angiotensin receptor antagonist widely used in the treatment of high blood pressure. This prodrug is metabolised into candesartan, which blocks the receptors AT1 for angiotensin II decreasing the blood pressure levels. During the development of a solid phase extraction procedure for the chromatographic determination of eight antihypertensive compounds, lack of linearity and reproducibility was observed only for candesartan cilexetil. Due to this fact, a stability study for this prodrug was performed. It showed that the lack of linearity and reproducibility was based on hydrolysis and transesterification processes which occurred during the drying step after elution with methanol into glass tubes. These phenomena could be reproduced artificially under basic conditions, which demonstrated the presence of basic residues in glass tubes. The study of this potential hydrolysis and transesterification reactions is very important to assure that labile drugs containing ester groups remain unaffected.
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http://dx.doi.org/10.1016/j.jchromb.2007.04.009DOI Listing
August 2007

Optimization via experimental design of an SPE-HPLC-UV-fluorescence method for the determination of valsartan and its metabolite in human plasma samples.

J Sep Sci 2006 Oct;29(15):2265-83

Kimika Analitikoaren Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea/UPV, Bilbo, Basque Country, Spain.

A chemometric approach was applied for the optimization of the extraction and separation of the antihypertensive drug valsartan and its metabolite valeryl-4-hydroxy-valsartan from human plasma samples. Due to the high number of experimental and response variables to be studied, fractional factorial design (FFD) and central composite design (CCD) were used to optimize the HPLC-UV-fluorescence method. First, the significant variables were chosen with the help of FFD; then, a CCD was run to obtain the optimal values for the significant variables. The measured responses were the corrected areas of the two analytes and the resolution between the chromatographic peaks. Separation of valsartan, its metabolite valeryl-4-hydroxy-valsartan and candesartan M1, used as internal standard, was made using an Atlantis dC18 100 mm x 3.9 mm id, 100 angstroms, 3 microm chromatographic column. The mobile phase was run in gradient elution mode and consisted of ACN with 0.025% TFA and a 5 mM phosphate buffer with 0.025% TFA at pH 2.5. The initial percentage of ACN was 32% with a stepness of 4.5%/min to reach the 50%. A flow rate of 1.30 mL/min was applied throughout the chromatographic run, and the column temperature was kept to 40+/-0.2 degrees C. In the SPE procedure, experimental design was also used in order at achieve a maximum recovery percentage and extracts free from plasma interferences. The extraction procedure for spiked human plasma samples was carried out using C8 cartridges, phosphate buffer (pH 2, 60 mM) as conditioning agent, a washing step with methanol-phosphate buffer (40:60 v/v), a drying step of 8 min, and diethyl ether as eluent. The SPE-HPLC-UV-fluorescence method developed allowed the separation and quantitation of valsartan and its metabolite from human plasma samples with an adequate resolution and a total analysis time of 1 h.
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http://dx.doi.org/10.1002/jssc.200600093DOI Listing
October 2006

Multivariate optimisation of a cyclodextrin-assisted-capillary zone electrophoretic method for the separation of torasemide and its metabolites.

J Chromatogr A 2003 Mar;990(1-2):271-9

Departamento de Química Analítica, Facultad de Ciencias, Universidad del País Vasco, Apdo. 644, 48080 Bilbao, Spain.

In this work, a rapid cyclodextrin-assisted capillary electrophoretic method is developed for the separation of the diuretic torasemide and three of its metabolites. Both fractional factorial and central composite designs were employed to optimise the separation method. The factors studied were pH, concentration of methyl-beta-cyclodextrin, concentration of the background electrolyte and percentage of acetonitrile as organic modifier. Monitored response was a composite quality response (Q*) which balanced conflicting normalized responses, such as resolution and migration time. Optimal separation of the four studied compounds was achieved in less than 6.5 min, using an electrolyte of 60 mM borate buffer with no organic modifier and 25 mM methyl-beta-cyclodextrin concentration adjusted to pH 8.0 at a potential of 30 kV. Detection wavelength and temperature were 197 nm and 20 degrees C respectively. This work means a significant improvement with regard to a previous separation method for these compounds developed in our laboratory.
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http://dx.doi.org/10.1016/s0021-9673(03)00055-4DOI Listing
March 2003

Determination of the angiotensin-converting enzyme inhibitor quinapril and its metabolite quinaprilat in pharmaceuticals and urine by capillary zone electrophoresis and solid-phase extraction.

Electrophoresis 2002 Jan;23(1):102-9

Departamento de Química Analítica, Facultad de Ciencias, Universidad del País, Vasco UPV/EHU, Bilbao, Spain.

Quinapril is an antihypertensive drug commonly used in the treatment of hypertension and congestive heart failure. In this work, a capillary zone electrophoresis system is optimized for the analysis of quinapril and its active metabolite quinaprilat in urine, as well as for the determination of the drug and its combination with hydrochlorothiazide in pharmaceuticals. The separation takes place in a fused-silica capillary. The running electrolyte consists of a 60 mM borate buffer solution, pH 9.5. The analysis of urine samples requires a previous extraction step using C8 solid-phase cartridges. Under the optimum experimental conditions, the separation of the two analytes and the internal standard takes less than 5 min. The detection limits obtained (75 and 95 ng/mL for quinapril and quinaprilat, respectively) allow the application of the electrophoretic method to the determination of the drug and its metabolite in urine samples obtained from four patients treated with quinapril.
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http://dx.doi.org/10.1002/1522-2683(200201)23:1<102::AID-ELPS102>3.0.CO;2-CDOI Listing
January 2002