Publications by authors named "Mario Contin"

19 Publications

  • Page 1 of 1

Elucidating an Atmospheric Brown Carbon Species-Toward Supplanting Chemical Intuition with Exhaustive Enumeration and Machine Learning.

Environ Sci Technol 2021 06 3;55(12):8447-8457. Epub 2021 Jun 3.

Faculty of Physics, University of Vienna, Kolingasse 14-16, AT-1090 Wien, Austria.

Brown carbon (BrC) is involved in atmospheric light absorption and climate forcing and can cause adverse health effects. Understanding the formation mechanisms and molecular structure of BrC is of key importance in developing strategies to control its environment and health impact. Structure determination of BrC is challenging, due to the lack of experiments providing molecular fingerprints and the sheer number of molecular candidates with identical mass. Suggestions based on chemical intuition are prone to errors due to the inherent bias. We present an unbiased algorithm, using graph-based molecule generation and machine learning, which can identify all molecular structures of compounds involved in biomass burning and the composition of BrC. We apply this algorithm to CHO, a light-absorbing "test case" molecule identified in chamber experiments on the aqueous photo-oxidation of syringol, a prevalent marker in wood smoke. Of the 260 million molecular graphs, the algorithm leaves only 36,518 (0.01%) as viable candidates matching the spectrum. Although no unique molecular structure is obtained from only a chemical formula and a UV/vis absorption spectrum, we discuss further reduction strategies and their efficacy. With additional data, the method can potentially more rapidly identify isomers extracted from lab and field aerosol particles without introducing human bias.
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http://dx.doi.org/10.1021/acs.est.1c00885DOI Listing
June 2021

Bioavailability of coenzyme Q loaded in an oleogel formulation for oral therapy: Comparison with a commercial-grade solid formulation.

Int J Pharm 2020 May 10;582:119315. Epub 2020 Apr 10.

Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAD Buenos Aires, Argentina; Member of CONICET, Argentina. Electronic address:

Coenzyme Q10 (CoQ) is essential in mitochondrial bioenergetics and is a potent endogenous antioxidant. Low CoQ levels are associated with neurodegenerative, metabolic, muscular and cardiovascular disorders. Early treatment with high doses (5-50 mg/kg/day) demonstrated to limit the onset and progression of neuropathology. Recently, we developed an oleogel matrix able to support a high dose of oil-dissolved CoQ, easy to swallow by CoQ-deficient patients who suffer from secondary dysphagia. In the present study, we evaluated the bioavailability of oleogel-dissolved CoQ and plasma antioxidant status in healthy adults in single-dose and repeated-dose studies. The single-dose study demonstrated that, in terms of CoQ bioavailability, 1 g CoQ/5g oleogel-disk was equivalent to the solid form (1 g CoQ/three 00-size-capsules), whereas the repeated-dose study (14-days-administration) demonstrated a significantly higher increase in plasma CoQ when administered through the oleogel, which could be compatible with the levels necessary to achieve an adequate therapeutic response. Also, a trend to a higher plasma apparent half-life (greater than24 h) was observed for the oleogel-loaded-CoQ. In conclusion, the oleogel matrix does not compromise the oil-dissolved CoQ bioavailability and can prevent the non-adherence to this vital supplementation in patients with high CoQ requirements. No significant variation in the plasma antioxidant status (vitamins A, E and C, glutathione and TBARs) was observed.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119315DOI Listing
May 2020

Development of carbohydrate functionalized magnetic nanoparticles for aminoglycosides magnetic solid phase extraction.

Anal Chim Acta 2019 Nov 24;1082:37-48. Epub 2019 Jul 24.

Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Intendente Güiraldes, 2160, Buenos Aires, PC:1428, Argentina; CONICET - Universidad de Buenos Aires, Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), Intendente Güiraldes, 2160, Buenos Aires PC:1428, Argentina. Electronic address:

Magnetic nanoparticles decorated with d-galactose and galactitol ([email protected] and [email protected]) were synthesized and employed as sorbent in a magnetic solid phase extraction (MSPE) procedure prior the analysis of aminoglycosides (AGs) in honey samples by LC-MS/MS. AGs are broad spectrum antibiotics, characterized by aminosugars, widespread used in therapeutic and veterinary applications. AGs can be found in the environment and food of animal origin. [email protected] and [email protected] were synthesized via copper catalyzed alkyne azide cycloaddition and the synthesis was efficiently followed by infrared spectroscopy. They were characterized by electron microscopy, thermogravimetric analysis and magnetization curves. The nature of the loading (acetonitrile:water, 50:50 v/v) and elution solution (formic acid 190 mM) were studied in order to optimize the MSPE. Quantitative difference between MSPE with [email protected] and MSPE with [email protected] in terms of recovery was found. The final optimized method using [email protected] and [email protected] was applied in the determination of AGs in honey. The MSPE performance of [email protected] was found to be superior to that of MSPE with [email protected] The limits of quantification were between 2 and 19 μg kg for amikacin, dihydrostreptomycin, tobramicyn and gentamycin. A good correlation between predicted and nominal values of AGs in honey was found (trueness from 84% to 109%). This MSPE procedure not only requires a minimum amount of sorbent (1 mg) and sample (0.2 g), but it can also be accomplish in a rather short time.
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http://dx.doi.org/10.1016/j.aca.2019.07.038DOI Listing
November 2019

Thioredoxin-1 is required for the cardioprotecive effect of sildenafil against ischaemia/reperfusion injury and mitochondrial dysfunction in mice.

Free Radic Res 2019 Oct 12;53(9-10):993-1004. Epub 2019 Sep 12.

Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET) , Buenos Aires , Argentina.

Sildenafil is a phosphodiesterase type 5 inhibitor which confers cardioprotection against myocardial ischaemia/reperfusion (I/R) injury. The aim of this study was to determine if Trx1 participates in cardioprotection exerted by sildenafil in an acute model of I/R, and to evaluate mitochondrial bioenergetics and cellular redox status. Langendorff-perfused hearts from wild type (WT) mice and a dominant negative (DN-Trx1) mutant of Trx1 were assigned to placebo or sildenafil (0.7 mg/kg i.p.) and subjected to 30 min of ischaemia followed by 120 min of reperfusion. WT + S showed a significant reduction of infarct size (51.2 ± 3.0% vs. 30 ± 3.0%, < .001), an effect not observed in DN-Trx. After I/R, sildenafil preserved state 3 oxygen consumption from WT, but had a milder effect in DN-Trx1 only partially protecting state 3 values. Treatment restored respiratory control (RC) after I/R, which resulted 8% (WT) and 24% (DN-Trx1) lower than in basal conditions. After I/R, a significant increase in HO production was observed both for WT and DN-Trx (WT: 1.17 ± 0.13 nmol/mg protein and DN-Trx: 1.38 ± 0.12 nmol/min mg protein). With sildenafil, values were 21% lower only in WT I/R. Treatment decreased GSSG levels both in WT and DN-Trx1. In addition, GSSG/GSH ratio was partially restored by sildenafil. Also, an increase in p-eNOS/eNOS even before the myocardial ischaemia was observed with sildenafil, both in WT (14%, > .05) and in DN-Trx (35%, < .05). Active Trx1 is required for the onset of the cardioprotective effects of sildenafil on I/R injury, together with the preservation of cellular redox balance and mitochondrial function.
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http://dx.doi.org/10.1080/10715762.2019.1661404DOI Listing
October 2019

Advances in drug delivery, gene delivery and therapeutic agents based on dendritic materials.

Future Med Chem 2019 07 1;11(14):1791-1810. Epub 2019 Aug 1.

Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1428EGA, Argentina.

Dendrimers are synthetic polymers that grow in three dimensions into well-defined structures. Their morphological appearance resembles a number of trees connected by a common point. Dendritic nanoparticles have been studied for a large number of pharmaceutical and biomedical applications including gene and drug delivery, clinical diagnosis and MRI. Despite the application of dendrimers, research is still in its childhood in comparison with liposomes and other nanomaterials. They are now playing a key role in several therapeutic strategies, with dendrimer-based products in clinical trials. The aim of this review is to describe the state-of-the-art of biomedical applications of dendrimers - and dendrimer conjugates - such as drug and gene delivery and antiviral activity.
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http://dx.doi.org/10.4155/fmc-2018-0452DOI Listing
July 2019

Modified ribavirin analogues as antiviral agents against Junín virus.

Bioorg Med Chem Lett 2019 02 2;29(4):556-559. Epub 2019 Jan 2.

CONICET - Universidad de Buenos Aires, Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), Intendente Güiraldes 2160, Buenos Aires PC:1428, Argentina; Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Intendente Güiraldes 2160, Buenos Aires PC:1428, Argentina. Electronic address:

In this work, several ribavirin analogues were synthesized and incorporated into a multivalent arrangement. Both were subsequently modified by the addition of polyhydroxylated residues. Their antiviral activity was tested against Junín virus, etiological agent responsible of Argentine hemorrhagic fever. Some compounds inhibited Junín virus in the range of 13.2-389.1 µM. Two modified ribavirin analogues presented an effective concentration comparable to ribavirin but with a higher selectivity index.
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http://dx.doi.org/10.1016/j.bmcl.2018.12.063DOI Listing
February 2019

Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis.

Cell Death Dis 2018 02 2;9(2):140. Epub 2018 Feb 2.

Departamento de Química Biológica, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Laboratorio de inflamación y Cáncer, Buenos Aires, Argentina.

An abrupt increase in metastatic growth as a consequence of the removal of primary tumors suggests that the concomitant resistance (CR) phenomenon might occur in human cancer. CR occurs in murine tumors and ROS-damaged phenylalanine, meta-tyrosine (m-Tyr), was proposed as the serum anti-tumor factor primarily responsible for CR. Herein, we demonstrate for the first time that CR happens in different experimental human solid tumors (prostate, lung anaplastic, and nasopharyngeal carcinoma). Moreover, m-Tyr was detected in the serum of mice bearing prostate cancer (PCa) xenografts. Primary tumor growth was inhibited in animals injected with m-Tyr. Further, the CR phenomenon was reversed when secondary implants were injected into mice with phenylalanine (Phe), a protective amino acid highly present in primary tumors. PCa cells exposed to m-Tyr in vitro showed reduced cell viability, downregulated NFκB/STAT3/Notch axis, and induced autophagy; effects reversed by Phe. Strikingly, m-Tyr administration also impaired both, spontaneous metastasis derived from murine mammary carcinomas (4T1, C7HI, and LMM3) and PCa experimental metastases. Altogether, our findings propose m-Tyr delivery as a novel approach to boost the therapeutic efficacy of the current treatment for metastasis preventing the escape from tumor dormancy.
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http://dx.doi.org/10.1038/s41419-017-0147-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833805PMC
February 2018

New Micellar Electrokinetic Chromatographic Method for Analyzing Idebenone in Pediatric Formulations.

J Chromatogr Sci 2017 03;55(3):351-357

Department of Pharmaceutical Technology.

A novel, simple and reliable method based on micellar electrokinetic chromatography with ultraviolet detection was developed to analyze idebenone in a pediatric formulation. Idebenone is a synthetic short chain benzoquinone that acts as an electron carrier in the mitochondrial electron transport chain facilitating the production of adenosine triphosphate. It can be found in two different redox states that differ in their physiological properties. Idebenone has been investigated as a treatment in several neurological disorders like Friedreich's ataxia, Leber's hereditary optic neuropathy, mitochondrial encephalomyopathies and senile dementia. Accordingly, a micellar electrokinetic chromatography was employed to discriminate both redox forms. The final optimized system was validated in terms of selectivity, linearity (r2 0.992), limit of detection (0.5 µg/mL), limit of quantification (1.8 µg/mL), intra- and inter-day precision (RSD ≤ 2) and accuracy in terms of recovery studies (99.3-100.5%). Robustness was studied following a Plackett-Burman design. Finally, the validated system was applied to the analysis of idebenone in a pediatric formulation.
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http://dx.doi.org/10.1093/chromsci/bmw172DOI Listing
March 2017

Synthesis and characterization of molecularly imprinted polymer nanoparticles for coenzyme Q10 dispersive micro solid phase extraction.

J Chromatogr A 2016 Jul 27;1456:1-9. Epub 2016 May 27.

Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Tecnológicas, CONICET, Buenos Aires, Argentina. Electronic address:

Molecularly imprinted polymer nanoparticles (MIPNPs) with the ability to recognize coenzyme Q10 (CoQ10) were synthesised in order to be employed as sorbent in a dispersive micro-solid phase extraction (DMSPE) for the determination of CoQ10 in a liver extract. CoQ10 is a redox-active, lipophilic substance integrated in the mitochondrial respiratory chain which acts as an electron carrier, shuttling electrons from complex I (NADH-ubiquinone oxidoreductase) and II (succinate-ubiquinone oxidoreductase) to complex III (ubiquinol-cytochrome c reductase), for the production of cellular energy. The MIPNPs were synthesised by precipitation polymerization using coenzyme Q0 as the dummy template, methacrylic acid as the functional monomer, an acetonitrile: water mixture as the porogen, ethylene glycol dimethacrylate as the crosslinker and potassium persulfate as initiator. The nanoparticles were characterized by microscopy, capillary electrophoresis, dynamic light scattering, N2 adsorption-desorption isotherms, and infrared spectroscopy. The MIPNPs demonstrated the presence of selective cavities complementary to the quinone nucleus of CoQ10, leading to a specific recognition of CoQ10 compared with related compounds. In the liver extract the relative CoQ10 peak area (CoQ10 area/total peak area) increased from 4.6% to 25.4% after the DMSPE procedure. The recovery percentage of CoQ10 from the liver matrix was between 70.5% and 83.7% quantified against CoQ10 standard processed under the same conditions. The DMSPE procedure allows the elution of almost all the CoQ10 retained (99.4%) in a small volume (200μL), allowing the sample to be concentrated 2.5 times (LOD: 1.1μgg(-1) and LOQ: 3.7μgg(-1) of tissue). The resulted clean up of the sample, the improvement in peak shape and baseline and the reduction of interferences, evidence that the MIPNPs could potentially be applied as sorbent in a DMSPE with satisfactory results and with a minimum amount of sorbent (1mg).
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http://dx.doi.org/10.1016/j.chroma.2016.05.091DOI Listing
July 2016

New analytical strategies applied to the determination of Coenzyme Q10 in biological matrix.

Methods Mol Biol 2015 ;1208:409-20

Department of Analytical Chemistry, Faculty of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.

In the last few years the importance of Coenzyme Q10 (CoQ10) determination has gained clinical relevance. CoQ10 is a redox-active, lipophilic substance integrated in the mitochondrial respiratory chain which acts as an electron carrier for the production of cellular energy. In addition, it is recognized as a primary regenerating antioxidant playing an intrinsic role against oxidative damage. There are some reports of low CoQ10 levels in a number of disorders, such as cancer, muscular, neurodegenerative, cardiological, and reproductive diseases. Therefore, it is a priority to develop analytical methodologies for evaluating CoQ10 in matrices of greater importance for the correct diagnosis of diseases, simple enough to be used in routine clinical laboratories. In this chapter two recently developed techniques, capillary electrophoresis and microHPLC, for the analysis of CoQ10 in biological matrices, are studied.
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http://dx.doi.org/10.1007/978-1-4939-1441-8_29DOI Listing
June 2015

The use of coenzyme Q0 as a template in the development of a molecularly imprinted polymer for the selective recognition of coenzyme Q10.

Anal Chim Acta 2014 Jan 21;807:67-74. Epub 2013 Nov 21.

Consejo Nacional de Investigaciones Científicas y Tecnológicas, CONICET, Buenos Aires, Argentina; Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. Electronic address:

In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 μL of sample mixed with 30 mg of MIP and 600 μL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 μg g(-1), respectively, and a linear range between 7.5 and 150 μg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix.
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http://dx.doi.org/10.1016/j.aca.2013.11.030DOI Listing
January 2014

Coenzyme Q in pregnant women and rats with intrahepatic cholestasis.

Liver Int 2014 Aug 2;34(7):1040-8. Epub 2013 Oct 2.

Analytical Chemistry, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina.

Background & Aims: Intrahepatic cholestasis of pregnancy is a high-risk liver disease given the eventual deleterious consequences that may occur in the foetus. It is accepted that the abnormal accumulation of hydrophobic bile acids in maternal serum are responsible for the disease development. Hydrophobic bile acids induce oxidative stress and apoptosis leading to the damage of the hepatic parenchyma and eventually extrahepatic tissues. As coenzyme Q (CoQ) is considered an early marker of oxidative stress in this study, we sought to assess CoQ levels, bile acid profile and oxidative stress status in intrahepatic cholestasis.

Methods: CoQ, vitamin E and malondialdehyde were measured in plasma and/or tissues by HPLC-UV method whereas serum bile acids by capillary electrophoresis in rats with ethinyl estradiol-induced cholestasis and women with pregnancy cholestasis.

Results: CoQ and vitamin E plasma levels were diminished in both rats and women with intrahepatic cholestasis. Furthermore, reduced CoQ was also found in muscle and brain of cholestatic rats but no changes were observed in heart or liver. In addition, a positive correlation between CoQ and ursodeoxycholic/lithocholic acid ratio was found in intrahepatic cholestasis suggesting that increased plasma lithocholic acid may be intimately related to CoQ depletion in blood and tissues.

Conclusion: Significant CoQ and vitamin E depletion occur in both animals and humans with intrahepatic cholestasis likely as the result of increased hydrophobic bile acids known to produce significant oxidative stress. Present findings further suggest that antioxidant supplementation complementary to traditional treatment may improve cholestasis outcome.
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http://dx.doi.org/10.1111/liv.12323DOI Listing
August 2014

The importance of analytical methodology in accurate diagnosis and monitoring of intrahepatic cholestasis of pregnancy.

Int J Gynaecol Obstet 2013 Oct 31;123(1):78-9. Epub 2013 Jul 31.

Department of Analytical Chemistry and Physicochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.

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http://dx.doi.org/10.1016/j.ijgo.2013.06.012DOI Listing
October 2013

Bile acids content in brain of common duct ligated rats.

Ann Hepatol 2012 Nov-Dec;11(6):930-4

School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.

Introduction: Cholestasis leads to liver cell death, fibrosis, cirrhosis, and eventually liver failure. Bile duct ligated rats constitute an interesting model to study the mechanism of cholestasis, and its action on several organs and tissues, including the brain.

Aim: To analyze brain bile acids individually in ligated rats to evaluate if its profile is altered towards a more toxic condition in cholestasis.

Material And Methods: Male Wistar rats were used and separated in two groups: bile duct ligated rats and sham operated rats (n = 5 in each group). Bile acid profile was assessed in brain homogenates. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase determinations, bilirubin and ammonia plasma concentration were also measured in both groups.

Results: Although the total amount of bile acids in control animal brains showed a higher concentration than in bile duct ligated rats, the bile acid profile in this group was found more toxic composition than in controls. Lithocholic acid was present in brain in higher concentration (87.4 % of total brain bile acids) in ligated rats and absent in controls. Alkaline phosphatase, bilirubin and ammonia were significantly higher in bile duct ligated rats than in control group.

Conclusion: It was found a toxic brain bile acid profile during hepatic cholestasis which could be one of the explanations of hepatic encephalopathy observed in cholestatic diseases.
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April 2013

In search of an accurate evaluation of intrahepatic cholestasis of pregnancy.

Scientifica (Cairo) 2012 1;2012:496489. Epub 2012 Aug 1.

Department of Analytical Chemistry and Physicochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina.

Until now, biochemical parameter for diagnosis of intrahepatic cholestasis of pregnancy (ICP) mostly used is the rise of total serum bile acids (TSBA) above the upper normal limit of 11 μM. However, differential diagnosis is very difficult since overlapped values calculated on bile acids determinations, are observed in different conditions of pregnancy including the benign condition of pruritus gravidarum. The aim of this work was to determine the better markers in ICP for a precise diagnosis together with parameters associated with severity of symptoms and treatment evaluation. Serum bile acid profiles were evaluated using capillary electrophoresis in 38 healthy pregnant women and 32 ICP patients and it was calculated the sensitivity, specificity, accuracy, predictive values and the relationships of certain individual bile acids in pregnant women in order to replace TSBA determinations. The evaluation of the results shows that LCA and UDCA/LCA ratio provided information for a more complete and accurate diagnosis and evaluation of ICP than calculation of solely TSBA levels in pregnant women.
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http://dx.doi.org/10.6064/2012/496489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820586PMC
November 2013

Simultaneous determination of nine endogenous steroids in human urine by polymeric-mixed micelle capillary electrophoresis.

Electrophoresis 2010 Oct;31(19):3305-13

Department of Analytical Chemistry and Physicochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.

A new CE system based on the use of polymeric-mixed micelles (cholic acid, SDS and the poloxamine Tetronic(®) 1107) was developed for the simultaneous determination of nine steroids in human urine. This method allows the baseline separation and quantitation of cortisol, androstenedione, estriol, dehydroepiandrosterone sulfate, testosterone, dehydroepiandrosterone, estrone, progesterone and estradiol in less than 25 min showing to be sensitive enough to detect low concentrations of these steroids in urine samples (5-45 ng/mL). The optimized electrophoretic conditions were performed using a 50 cm × 75 μm capillary, 18 kV, 25°C, with 44 mM cholic acid, 10 mM SDS, 0.05% w/v tetronic(®) 1107, 2.5% v/v methanol, 2.5% v/v tetrahydrofuran in 5 mM borate - 5 mM phosphate buffer (pH=8.0) as a background electrolyte and a dual 210/254 UV-detection. The method can simultaneously determine 0.1-120 μg/mL, which corresponds to 5-6000 ng/mL of steroids in 2 mL urine. The recoveries ranged between 82.4 and 101.5%. Due to its simplicity, speed, accuracy and reliability, the proposed method could be a potential alternative to the traditional methodologies used with clinical purposes.
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http://dx.doi.org/10.1002/elps.201000096DOI Listing
October 2010

Novel and highly sensitive mixed-polymeric electrokinetic chromatography system for determination of contaminants and impurities of heparin samples.

Electrophoresis 2010 Oct;31(21):3606-12

Department of Analytical Chemistry and Physicochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.

A mixed-polymeric electrokinetic chromatography system has been developed for the simultaneous determination of a contaminant like oversulfated condroitin sulfate (OSCS) and impurities expressed as dermatan (Der) in heparin (Hep) samples. The EKC system consisted of 0.5% w/v polymeric β-CD, 0.4% w/v tetronic(®) 1107 and 400 mM tris-phosphate buffer at pH 3.5. The optimized electrophoretic conditions included the use of an uncoated-silica capillary of 50 cm of total length and 75 μm id, an applied voltage of -7 kV, a temperature of 30°C and 200 nm UV-detection. The highly sensitive method developed showed low values of LOD, 0.07% w/w (0.07 μg/mL) (OSCS) and 0.1% w/w (0.1 μg/mL) (Der), and values of LOQ 0.2% w/w (0.2 μg/mL) (OSCS) and 0.3% w/w (0.3 μg/mL) (Der) with a concentration level of Hep sample as low as 0.1 mg/mL. Additional parameters of validation such as specificity, linearity, accuracy, and robustness were evaluated according to international guidelines. Owing to its simplicity, high sensitivity, and reliability, the proposed method can be an advantageous alternative to the traditional methodologies for the analysis of Hep in raw material and specially in finished products because of the low amounts of Hep sample required.
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http://dx.doi.org/10.1002/elps.201000296DOI Listing
October 2010

A capillary electrophoretic system based on a novel microemulsion for the analysis of coenzyme Q10 in human plasma by electrokinetic chromatography.

Electrophoresis 2009 Jun;30(11):1899-905

Consejo Nacional de Investigaciones Científicas y Tecnológicas, CONICET, Argentina.

A new analytical method for determination of coenzyme Q10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CoQ10) in human plasma was developed based on CE using a double tensioactive microemulsion. CoQ10 was quantitatively extracted into 1-propanol/hexane and quantified by MEEKC. The microemulsion was prepared by mixing 1.4% w/w sodium bis(2-ethylhexyl) sulfosuccinate, 4% w/w cholic acid, 1% w/w octane, 8.5% w/w butanol, 0.1% w/w PVA and 85% w/w 10 mM Tris buffer at pH 9.0. The optimized electrophoretic conditions included the use of an uncoated silica capillary of 60 cm total length and 75 mum id, an applied voltage of 20 kV, room temperature and 214 nm ultraviolet detection. Selectivity, linearity, LOD, LOQ, precision and accuracy were evaluated as the parameters of validation. Owing to its simplicity and reliability, the proposed method can be an advantageous alternative to the traditional methodology for the quantitation of CoQ10 in human plasma with good accuracy and precision.
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http://dx.doi.org/10.1002/elps.200800783DOI Listing
June 2009

Lithocholic acid as a biomarker of intrahepatic cholestasis of pregnancy during ursodeoxycholic acid treatment.

Ann Clin Biochem 2009 Jan;46(Pt 1):44-9

Cathedra of Analytical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.

Background: The diagnosis and treatment of intrahepatic cholestasis of pregnancy (ICP) has important implications on fetal health. The biochemical parameter commonly used in the diagnosis of ICP is the determination of the concentration of total serum bile acids (TSBA). However, bile acid profile, especially lithocholic acid (LCA) analysis is a more sensitive and specific biomarker for differential diagnosis of this pathology and also could be an alternative to evaluate the efficiency of ursodeoxycholic acid (UDCA) for ICP treatment.

Methods: Serum bile acid (SBA) profiles including LCA determination, were studied in 28 ICP patients using a capillary electrophoresis method. The effects of UDCA treatment on bile acid profile, were analysed in 23 out of 28 ICP patients and the two samples obtained before and 15 days after treatment were compared. Two samples taken as controls were also obtained from each of five patients without therapy.

Results: A dramatic decrease in LCA concentrations and maintenance of TSBA concentrations were found in all patients after UDCA therapy, whereas SBA profiles together with LCA values did not change in patients without therapy.

Conclusion: We propose LCA as an alternative biomarker and a more sensitive parameter than TSBA to evaluate the effectiveness of UDCA treatment, at least in ICP patients from Argentina.
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http://dx.doi.org/10.1258/acb.2008.008130DOI Listing
January 2009
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