Biomedical subjects

S Sagrado

Publications and source records attributed to S Sagrado.

35 records · Page 2Linked to original sources

PubMed2002

Opioid analgetics retention-pharmacologic activity models using biopartitioning micellar chromatography.

Opioids are drugs used in medicine for pain control. In this paper, retention-pharmacokinetics and retention-pharmacodynamics relationships of opioids are proposed and statistically validated. These models are based on the compound retention in the biopartitioning micellar chromatography system (BMC), a new methodology which has successfully been used to develop QRAR models for many other families of compounds. The obtained results are compared to the traditional QSAR models using lipophilicity data. The adequacy of QRAR models is due to the fact that the characteristics of the compounds such as the hydrophobicity, electronic charge and steric effects determine both their retention in BMC and their pharmacokinetic and pharmacodynamic behavior.

Analgesics, Opioid↗

PubMed2002

QRAR models for central nervous system drugs using biopartitioning micellar chromatography.

The capability of biopartitioning Micellar Chromatography, BMC, to describe and estimate pharmacokinetic and pharmacodynamic parameters of central nervous system drugs is reviewed in this article. BMC is a mode of micellar liquid chromatography, MLC, that uses micellar mobile phases of Brij35 (polyoxyethilene(23) lauryl ether) prepared in physiological conditions (pH, ionic strength). The retention of a drug in this system depends on its hydrophobic, electronic and steric properties, which also determine its biological activity. The results of BMC studies suggest that this in vitro approach is an attractive useful tool to be implemented into the lead optimization step of drug development scheme.

Animals↗

PubMed2001

Retention pharmacokinetic and pharmacodynamic parameter relationships of antihistamine drugs using biopartitioning micellar chromatography.

Antihistamines are drugs which act by competitive inhibition of the H1 or H2 histamine receptors. Little has been known about their clinical pharmacokinetics and biological responses until the last few years. In this paper, we propose quantitative retention-activity relationship, QRAR, models based on the retention data of antihistamines in a biopartitioning micellar chromatography (BMC) system using a Brij35 mobile phase for describing pharmacokinetic parameters such as half-life and volume of distribution, or the pharmacodynamic parameters, therapeutic plasma levels, lethal doses and drug-receptor dissociation constant. The predictive ability of these models is statistically validated. These results are compared to traditional quantitative structure-activity relationship, QSAR, models using lipophilicity data. The adequacy of QRAR models can be explained taking into account the fact that the retention of compounds in BMC depends on their hydrophobic, electronic and steric characteristics which are of great importance in pharmacokinetic and pharmacodynamic behavior.

Chromatography, Liquid↗

PubMed2001

Retention-property relationships of anticonvulsant drugs by biopartitioning micellar chromatography.

Epilepsy may be considered as a group of disorders with only one thing in common: the fact that recurrent anomalous electrochemical phenomena appear in the central nervous system. Different classes of drugs are included under the generic term of anticonvulsant drugs. All of them work by decreasing discharge propagation in different ways. Biopartitioning micellar chromatography (BMC) is a mode of reversed-phase liquid chromatography, which can be used as an in vitro system to model the biopartitioning process of drugs when there are no active processes. In this paper, relationships between the BMC retention data of anticonvulsant drugs, their pharmacokinetics (oral absorption, protein binding, volume of distribution, clearance, and renal elimination) and their therapeutic parameters (therapeutic, toxic and comatose-fatal concentration, and LD50) are studied and the predictive ability of models is evaluated.

Anticonvulsants↗

PubMed2001

Biopartitioning micellar chromatography: an in vitro technique for predicting human drug absorption.

The main oral drug absorption barriers are fluid cell membranes and generally drugs are absorbed by a passive diffusion mechanism. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to mimic the drug partitioning process in biological systems. In this paper the usefulness of BMC for predicting oral drug absorption in humans is demonstrated. A hyperbolic model has been obtained using the retention data of a heterogeneous set of 74 compounds, which shows predictive ability for drugs absorbed by passive diffusion. The model obtained in BMC is compared with those obtained using the well-known systems (Caco-2 and TC-7) that use intestinal epithelium cell lines. The use of BMC is simple, reproducible and can provide key information about the transport properties of new compounds during the drug discovery process.

Administration, Oral↗

PubMed2001

Development of predictive retention-activity models of butyrophenones by biopartitioning micellar chromatography.

The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that in adequate experimental conditions the solute partitioning into the chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis of drug and metabolite uptake, passive transport across membranes and bioaccumulation. The use of retention data obtained in biopartitioning micellar chromatography (BMC) has been demonstrated to be helpful in describing the biological behaviour of different kinds of drugs. In this chromatographic system, polioxyethylene 23 lauryl ether Brij35 micellar mobile phases and C(18) reversed stationary phase in adequate experimental conditions are used. The RP-HPLC capacity factors of butyrophenones were determined using different Brij35 concentrations as micellar mobile phases. Relationships between seven biological activities of butyrophenones reported in bibliography and retention data were established and their predictive and interpretative ability evaluated. These relationships were significant between preclinical pharmacology and therapeutic efficacy parameters and the retention factors of butyrophenones (0.89 < R(2) < 0.98). The results indicate that the retention of compounds in BMC is capable of describing and predicting in vitro the biological activities of butyrophenones. This approach can be very useful in the development of new neuroleptic drugs, avoiding the use of experimental animals.

Animals↗

PubMed2001

Multivariate data analysis of quality parameters in drinking water.

The quality of water destined for human consumption has been treated as a multivariate property. Since most of the quality parameters are obtained by applying analytical methods, the routine analytical laboratory (responsible for the accuracy of analytical data) has been treated as a process system for water quality estimation. Multivariate tools, based on principal component analysis (PCA) and partial least squares (PLS) regression, are used in the present paper to: (i) study the main factors of the latent data structure and (ii) characterize the water samples and the analytical methods in terms of multivariate quality control (MQC). Such tools could warn of both possible health risks related to anomalous sample composition and failures in the analytical methods.

Multivariate Analysis↗

PubMed2000

Development of predictive retention-activity relationship models of non-steroidal anti-inflammatory drugs by micellar liquid chromatography: comparison with immobilized artificial membrane columns.

The predictive and interpretative capability of quantitative chromatographic retention-biological activity models is supported by the fact that under adequate experimental conditions the solute partitioning into chromatographic system can emulate the solute partitioning into lipid bilayers of biological membranes, which is the basis for drug and metabolite uptake, passive transport across membranes and bioaccumulation. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict some biological activities of different kinds of drugs. In this study, quantitative retention-activity relationship (QRAR) models to describe some of the biological activities and pharmacokinetic properties of non-steroidal anti-inflammatory drugs (NSAIDs) with predictive and interpretative ability are obtained. These models are compared with those obtained using immobilized artificial membrane (IAM) column data taken from the literature. For NSAIDs, the statistical characteristics of the micellar liquid chromatography (MLC) QRAR models were better than or at least comparable to those of the IAM-QRAR models.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Micellar liquid chromatography for prediction of drug transport.

The vast majority of well absorbed drugs are transported passively across the cell membranes. Physicochemical descriptors of drug molecules that are believed to influence transcellular transport are routinely used to predict drug absorption by means of complex mathematical models. In this paper, a new in vitro method, based on the retention data in micellar liquid chromatography (MLC), is validated for the prediction of passive drug absorption. The retention of a heterogeneous drugs set in MLC using Brij 35 as surfactant in the mobile phase is compared with the retention data reported in literature obtained in red cell membrane lipid liposomes, human red cell membranes vesicles (vesicles), native membranes of adsorbed red cells (ghosts) and egg phospholipids liposomes [Beigi et al., Int. J. Pharm., 164 (1998) 129-137]. Finally, the correlation between the logarithm of retention factors in MLC and reported oral drug absorption values for barbiturates and beta-blockers is studied. Predictive regression models for estimating oral drug absorption using the logarithm of the retention values as independent variable are proposed.

Administration, Oral↗

PubMed2000

Determination of phenobarbital in plasma by micellar liquid chromatography.

A new liquid chromatographic procedure for the determination of phenobarbital in plasma samples is described. The proposed system uses a Spherisorb octadecyl-silane ODS-2 C(18) analytical column, a guard column of similar characteristics, and a 0.03 M CTAB-3% 1-propanol at pH 7 mobile phase. The UV detector was set at 250 nm. Butabarbital was used as internal standard. Sample preparation only required the addition to the plasma samples of a 0.1 M SDS solution at pH 3 and centrifugation before injection into the chromatographic system. The limit of detection was 0.83 microg/mL of phenobarbital in plasma samples. The coefficients of variation were lower than 7. 5%.

Chromatography, Liquid↗

PubMed2000

Determination of amobarbital and secobarbital in plasma samples using micellar liquid chromatography.

A new liquid chromatographic procedure for the determination of amobarbital and secobarbital in plasma samples is proposed. The method uses a Spherisorb octadecylsilane ODS-2 C(18) analytical column, a guard column of similar characteristics and 0.04 M CTAB solution buffered at pH 7.5 containing 3% 1-propanol as micellar mobile phase. The UV detection was carried out at 250 nm. Butabarbital was used as internal standard. Plasma samples preparation only required adequate dilution with the mobile phase before injection into the chromatographic system. The limits of detection were 0.2 and 0.4 mg/L for amobarbital and secobarbital, respectively. The proposed method allows the determination of amobarbital and secobarbital in plasma at therapeutic levels.

Amobarbital↗

PubMed1999

Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.

The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.

Adenylyl Cyclase Inhibitors↗

PubMed1999

Retention-activity relationship studies of benzodiazepines by micellar liquid chromatography.

Solute partitioning into lipid bilayers of biological membranes is the basis for drug and metabolite uptake, passive transport across membranes and bioaccumulation. In order to emulate in vitro the partitioning process in the biomembranes, different approaches have been proposed. The use of micellar solutions as mobile phases in reversed-phase liquid chromatography (micellar liquid chromatography, MLC) has proven to be valid in the prediction of the biological activities of local anesthetics, catecholamines and barbiturates. In this paper we focus our attention on benzodiazepines. The retention of benzodiazepines using different concentrations of Brij35 as micellar mobile phase in modified C(18) stationary phase was studied. Quantitative retention-activity relationships (QRAR) in MLC were investigated for these compounds. An adequate correlation between the capacity factors (log k) and the toxicity (log LD(50)) and anxiolitic activity (log ED(50)) of benzodiazepines was obtained.

Benzodiazepines↗

PubMed1999

Development of predictive retention-activity relationship models of antipsychotic drugs by micellar liquid chromatography.

Animals↗

PubMed1999

Determination of barbiturates in urine by micellar liquid chromatography and direct injection of sample.

A liquid chromatographic procedure for the determination of six barbiturates (barbital, diallyl barbituric acid, phenobarbital, butabarbital, amobarbital and pentobarbital) in urine samples is described. The proposed system uses a Spherisorb octadecyl-silane ODS-2 C18 analytical column and a guard column of similar characteristics. The UV detector was set at 240 nm. A study to select adequate composition of the micellar mobile phase for the separation of these compounds in urine samples is performed. Maximum resolution was achieved with a 0.07 M sodium dodecylsulphate-0.3% propanol at pH 7.4 eluent. Limits of detection at 240 nm were ranged between 0.13 microg ml(-1) for diallyl barbituric acid and 2.7 microg ml(-1) for amobarbital. The procedure allows for the determination of these compounds in 20 minutes, it does not require prior a sample preparation step and it can be very useful to the investigation of intoxication.

1-Propanol↗

PubMed1997

Reliability of the capacity factor at zero micellar concentration and the solute-micelle association constant estimates by micellar liquid chromatography.

In micellar liquid chromatography, MLC, the hydrophobicity of a compound is the predominant effect on its retention and interaction with micelles. The capacity factors at zero micellar concentration, k(m), and the solute-micelle association constants, KAM- have recently been used as the hydrophobicity index of compounds and are important in QSAR studies. These parameters could be estimated (by regression) from the (k,[M]) data, where k is the capacity factor and [M] the surfactant concentration minus the critical micelle concentration. km and KAM are usually obtained from the intercept and slope, respectively, of the plot 1/k vs. [M]. In spite of the general use of this equation, the reliability of the estimates has not received special attention. Two new regression models have been proposed: a nonlinear model (plot k vs. [M]) and a new linear model (k vs. k.[M]). The reliability of the km and KAM estimates is studied with the aid of simulated data, and the conclusions obtained from the theoretical study are contrasted with experimental data. The influence of variables like the hydrophobicity of compounds, the KAM/km ratio, the uncertainty of experimental k data and the experimental design have been considered. Some critical aspects of the models and recommendations for their use are provided.

Chromatography, Liquid↗

PubMed1997

Simultaneous spectrophotometric determination of calcium and magnesium in mineral waters by means of multivariate partial least-squares regression.

A method for simultaneous spectrophotometric determination of calcium and magnesium in mineral waters using multivariate calibration methods is proposed. The method is based on the development of the reaction between the analytes and Methylthymol Blue at pH 11. Two operational modes were used: static (spectral information) and flow injection (FI) (spectral and kinetic information). The selection of variables was studied. A series of synthetic solutions containing different concentrations of calcium and magnesium were used to check the prediction ability of the partial least-squares models. The method was applied to the analysis of mineral waters and the results were compared with those obtained by complexometry. No significant differences at the 95% confidence level were found. The proposed method is simple, accurate and reproducible, and it could be easily adapted as a portable (static mode) or automatic (FI) method.

Calcium↗