Determination of higenamine in dietary supplements by UHPLC/MS/MS method.

From 1st January 2017 higenamine was added on the WADA (World Anti-doping Agency) Prohibited list under S3 group beta-2 agonists as at all times banned substance for the athletes. The main origine of higenamine (or norcoclaurine) are different plants including Nandina domestica, Aconitum carmichaelii, Asarum heterotropioides, Galium divaricatum, Annona squamosa, Nelumbo nucifera etc. Higenamine main use is related to weight loss and it could be found (un)labeled in different dietary supplements. The objective of this study was development of sensitive and reliable UHPLC/MS/MS method for determination of higenamine in various dietary supplement samples. In order to obtain high method sensitivity, hydrophilic interaction liquid chromatography (HILIC) mode was applied. Separation was carried out on UHPLC Acquity BEH HILIC analytical column (2.1mm×100mm, 1.7µm particle size). Mobile phase consisted of 0.1% formic acid in water and acetonitrile, respectively, was mixed in ratio of 30:70, v/v. Flow rate was set at 0.2mLmin-1. Quercetin was used as an internal standard. ESI (+) source ionization mode using multi reaction monitoring (MRM) mode was utilized and three ion transitions of higenamine were followed 272.08→107.01, 272.08→161.07 and 272.08→77.08. Developed method was fully validated and applied for identification and quantification of higenamine in different dietary supplements. According to the results, the most of investigated supplements were free of higenamine, and on the other hand, presence of higenamine was confirmed in some samples while it was not declared on the label.

European Confederation of Medical Mycology (ECMM) epidemiological survey on invasive infections due to Fusarium species in Europe.

In order to better understand the epidemiology of fusariosis in Europe, a survey collecting information on the clinical characteristics of the patients infected by Fusarium as well as on the infecting isolates was launched. A total of 76 cases of invasive fusariosis occurring from January 2007 to June 2012 were collected and Fusarium isolates were identified by sequencing the translation elongation factor 1α (TEF) gene. Also, antifungal susceptibility was tested by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Etest. Disseminated disease was considered proven in 46 cases and probable in 17 cases. Localised infection was seen in 13 cases. Gibberella fujikuroi species complex (SC), including Fusarium verticillioides and F. proliferatum, and F. solani SC were the most frequent aetiology of disseminated and localised infections, respectively. The crude mortality rate was 46 %, the highest associated with F. solani SC (67 %) and F. proliferatum (62.5 %). A wide range of antifungal susceptibilities was observed. Amphotericin B was the most potent antifungal in vitro, and itraconazole the least effective. The azoles exhibited lower minimum inhibitory concentrations (MICs) against F. verticillioides strains, with posaconazole having a slightly better performance, while F. solani SC isolates were resistant to all three azoles tested. The essential agreement between the Etest and the EUCAST method was 100 % for itraconazole and voriconazole, and 96 % for amphotericin B and posaconazole. In conclusion, we confirm that fusariosis is a rare but severe event in Europe, that G. fujikuroi SC is the predominant cause of deep infections and that different species have different antifungal in vitro susceptibility patterns.

Predicción de porcentaje de masa adiposa a través de impedancia bio-eléctrica y método antropométrico / Mass adipose prediction percentage through biolectrical impedance and anthropometric method

Este estudio fue desarrollado con la finalidad de formular una ecuación de predicción de % de masa adiposa en valores antropométricos, a partir, de los valores predeterminados a través del instrumento de bioimpedancia TANITA. Esto basado en la premisa de que cada día ha aumentado la importancia sobre la estimación de la masa adiposa a nivel clínico, por lo cual se evaluó una población de 28 sujetos cuyo rango de edad fluctúa entre los 20-28 años, pertenecientes a la Escuela de Caballería Blindada de la ciudad de Quillota. Se realizaron las mediciones pertinentes para la estimación de masa adiposa a través de la bioimpedancia y la antropometría, cuyos resultados arrojaron diferencias significativas entre ambos métodos, obteniendo un coeficiente de correlación de Pearson de 0,34. Esto nos indica que al evaluar los criterios de homocedasticidad, linealidad, para generar una ecuación de estimación, no sería posible...

This case was developed with the objective of makes a prediction equation of adipose mass percent in values anthropometric, to star off the predetermined slant of instruments of impedance bioelectric TANITA. This is based in the premise that every day the importance of estimation about the fat mass in a clinic level, it is getting bigger and bigger, for this reason a population of twenty eight people with age range fluctuate among twenty to twenty eight was evaluated, they were part of "Escuela de Caballería Blindada" in the city of Quillota. The Pertinent measurements for the estimation of fatty mass were realized through of impedance bioelectric and anthropometry, the results made big differences between both methods, obtaining an index of correlation coefficient a 0.13 and a person correlation of 0.34. This suggests that possible creation does not accomplish with the criteria homescedasticity, in brief, this is unsafe...

Breast MRI: intraindividual comparative study at 1.5 and 3.0T; initial experience.

PURPOSE: To prospectively and intraindividually compare breast magnetic resonance imaging (MRI) at 1.5 Tesla (T) and 3.0T. METHODS: A prospective intraindividual Ethics Committee- approved study was performed in 31 women (average age 58.6±12.3 years), with 114 lesions (9 benign, 105 breast cancers; 24 patients with unilateral and 7 with bilateral cancers). Axial bilateral breast high-spatial resolution contrast-enhanced dynamic MRI was performed at 1.5T using 3 dimensional (3D) dynamic gradient-echo sequences in all patients (spatial resolution 1.1×0.7×2 mm; temporal resolution 41 sec per dynamic acquisition), and after 24-48 h at 3.0T (0.6×0.6×1.7 mm; temporal resolution 65 and 72 sec per dynamic acquisition). Contrast enhancement ratio, number and features of enhancing lesions, image quality and reliability were compared by two radiologists independently. RESULTS: 102 cancer lesions were detected at 1.5T and 105 cancer lesions were detected in 31 patients at 3.0T. One cancer lesion was observed at 1.5T which was missed at 3.0T, and 3 cancer lesions and one high-risk lesion (LCIS) were detected at 3.0T while missed at 1.5T. Enhancement rates were significantly higher at 1.5T (224.5±100.2) compared to 3.0T (133.7±38.3). Better image quality was observed at 3.0T. Interobserver reliability was higher at 3.0T (p= 0.684) compared to 1.5T (p= 0.351). CONCLUSION: Detection of breast cancer shows a trend of better performance at 3.0T than at 1.5T.

Advancement in optimization tactic achieved by newly developed chromatographic response function: application to LC separation of raloxifene and its impurities.

In this paper a new chromatographic response function (CRF) is designed and proposed for utilization in the optimization strategies. The function capability to represent the overall quality of a experimentally obtained chromatograms was compared to the other two objective functions and proved to give more accurate and reliable results. The new CRF has improved concept of separation and time term estimation. It reflects all important defects of the chromatogram such as the appearance of asymmetrical or overlapping peaks and prolonged elution time and allows the appropriate weighting of each of them. The LC separation of raloxifene and its four impurities was evaluated through the central composite design experimental plan choosing the new CRF to be the only output of the system. The function demonstrated the ability to judge the impact of the complex interactions of the selected chromatographic parameters (acetonitrile content in the mobile phase, sodium dodecyl sulfate concentration in the water phase, pH of the mobile phase and column temperature) on the mixture behavior and led to the determination of the optimal separation conditions. The newly developed CRF proved to have the advanced performances and it presents the important step forward in the optimization of the chromatographic separation.

Comparación entre dos métodos utilizados para medir la curva lumbar / Comparison of two method for measuring the lumbar curve

Las alteraciones posturales tales como hiperlordosis, aumento de la cifosis, cifolordosis y escoliosis en columna, producen complicaciones a nivel músculo-esquelético y articular. Debido a esto, es que en el último tiempo ha aumentado el número de atenciones kinésicas por patologías de la columna lumbar, he aquí la importancia de un test clínico que cuente con la confiabilidad necesaria para determinar la curvatura lumbar. El objetivo de este estudio es determinar si existen diferencias en los resultados entre los dos métodos utilizados para medir la curva lumbar: el test clínico de las flechas sagitales y el ángulo de la columna lumbar mediante radiografías. En una muestra de 32 pacientes de edad promedio 44,93 (+/- 12,67 años) evaluados en el Servicio de Kinesiología del Centro Médico Megasalud de Viña del Mar entre los meses de Marzo y Agosto del 2008. El procedimiento utilizado fue el examen clínico, en el cual se usó una plomada que va desde C7, pasando por la línea ínterglútea. En el plano sagital se mide la curvatura lumbar a nivel de L3. Para la medición del ángulo de la curvatura lumbar se utilizó una radiografía proyección lateral en la cual se proyectan las mesetas superior de L1 e inferior de L5 para la conformación del ángulo lumbar y su posterior medición. El resultado obtenido por medio del examen clínico entre el test de las flechas sagitales y las radiografías del ángulo de la lordosis lumbar para un índice de concordancia de Kappa, fue mayor o igual a un 95 por ciento. De esta manera, se obtuvo que el test de las flechas sagitales es una herramienta válida para la pesquisa de patologías lumbares, al igual que la radiografía, con una marcada diferencia en el costo económico entre ambas.

The altered posture, such as hiperlordosis, increase in kyphosis, and scoliosis in cifolordosis column complications occur at the muscular, skeletal and articulate. Because of this, is that in recent times to increase the number of benefits for kinesics pathologies of the lumbar spine, and here the importance of a clinical test that has the confidence necessary to determine lumbar curvature. The objective of the study seeks to determine whether there are differences in outcomes between the two methods used to measure the lumbar curve, the test of the arrows sagitales and the angle of the lumbar spine using x-rays in patients greater than or equal to 21 years, as assessed the service kinesiology of Centro Médico Megasalud of Viña del Mar, between the months of March and August 2008. The procedure used was by means of physical examination, which uses a plumb line that runs from C7 through inter gluteal line in the sagittal plane was measured at the lumbar curvature of L3 and compared with the measurement of the angle curvature of the lumbar measured by radiographic position in bipedal in a side view in 32 adults, measures of kinesiology at the service of the Medical Center Megasalud of Viña del Mar, Chile. The result obtained by means of physical examination between the test of the arrows sagitales versus the angle of the lumbar lordosis measured by X-rays, reached a record of correlation between the two diagnostic tests greater than or equal to 95 percent. In conclusion we can say that the test of the arrows sagitales is a valid tool for the investigation of lumbar pathologies, like radiography, with a marked difference in cost between the two.

Peso de nacimiento y posterior estado nutricional, desarrollo cognitivo y actividad ocupacional: una revisión crítica / Birth weight and later nutritional status, cognitive development and job status: a critical review

El impacto del estado nutricional prenatal, especialmente lo concerniente al peso de nacimiento (PN) y sus efectos tanto en el corto, mediano o largo plazo, sobre el estado nutricional y el desarrollo cognitivo del niño y, sobre la ocupación desempeñada en la vida adulta, ha sido una problemática de interés para diversos investigadores; al respecto, algunos autores encuentran una asociación positiva y significativa entre estas variables, mientras que otros no encuentran ninguna relación. Es así como se ha descrito que niños con PN insuficiente, bajo o, extremadamente bajo, además del deterioro temprano del estado nutricional, presentarían en el corto plazo, un mayor riesgo de daño en la maduración cerebral, retraso del desarrollo cognitivo y menores circunferencias craneanas, lo que implicaría menor volumen encefálico y bajo rendimiento intelectual. En el corto y mediano plazo, esta situación perjudicaría el proceso enseñanza-aprendizaje en la etapa escolar, mientras que en el largo plazo, esto condicionaría la ocupación a desempeñar en la vida adulta. Actualmente, el cuerpo de conocimientos pone de manifiesto que los hallazgos relativos a estas asociaciones no son concluyentes, existiendo gran controversia en estas materias. Este artículo de revisión tiene el propósito de analizar la evidencia existente hasta este momento, con el objeto de incentivar la investigación en estos aspectos que son de gran relevancia para el desarrollo del niño y su vida futura.

The impact of prenatal nutritional status, assessed through birth weight (BW) and their effects in the short, medium and long-term on nutritional status, cognitive development and job status in the adult life, has been a problem of interest for several researchers; as regards, some of these report a positive and significant association between these variables and others do not find any relation. Children with insufficient, low or very low BW despite the early more deteriorate nutritional status should present higher risk for brain maturation, failure cognitive development and lowered head circumference which implies both lowered brain volume and intellectual development. In the short and medium-term, this situation damages the learning process at school-age, while in the long-term this might condition the quality of jobs. At present, the body of knowledge pinpoints that findings related to these associations is not conclusive verifying a great controversy in these matters. This review article has the purpose of analyzing the current evidence, in order to stimulate research about to these aspects which are relevant for child development and their future life.

Artificial neural networks in analysis of indinavir and its degradation products retention.

Artificial neural networks (ANN) are biologically inspired computer programs designed to simulate the way in which the human brain processes the information. In the past few years, coupling of experimental design (ED) and ANN became useful tool in the method optimization. This paper presents the application of ED-ANN in analysis of chromatographic behavior of indinavir and its degradation products. According to preliminary study, full factorial design 2(4) was chosen to set input variables for network training. Experimental data (inputs) and results for retention factors from experiments (outputs) were used to train the ANN with aim to define correlation among variables. For networks training multi-layer perceptron (MLP) with back propagation (BP) algorithm was used. Network with the lowest root mean square (RMS) had 4-8-3 topology. Predicted data were in good agreement with experimental data (correlation was higher than 0.9713 for training set). Regression statistics confirmed good ability of trained network to predict compounds retention.

Chemometrical evaluation of ropinirole and its impurity's chromatographic behavior.

The aim of this study was the chemometrical evaluation of ropinirole and its impurity's (4-[2-(dipropylamino)ethyl]-1H-indol-2,3-dione) chromatographic behavior in systematic and the most efficient way. For that purpose, as very descriptive, response surface designs are most preferable. Face-centered central composite design (CCD) with 2(3) full factorial design, +/-1 star design and four replication in central point was applied for a response surface study, in order to examine in depth the effects of the most important factors. Factors-independent variables (acetonitrile content, pH of the mobile phase and concentration of sodium heptane sulfonate in water phase) were extracted from the preliminary study and as dependent variables five responses (retention factor of ropinirole, retentin factor of its impurity, resolution, symmetry of ropinirole peak and symmetry of impurity peak) were selected. For the improvement of method development and optimization step, Derringer's desirability function was applied to simultaneously optimize the five chosen responses. The procedure allowed deduction of optimal conditions and the predicted optimum was acetonitrile-5mM of sodium heptane sulfonate (21.6:78.4, v/v), pH of the mobile phase adjusted at 2.0 with ortho phosphoric acid. By calculating global desirability's determination coefficients (R(D)(2)), as well as by the visual inspection of 3D graphs for global desirability, robustness of the proposed method was also estimated.

[Birth weight and later nutritional status, cognitive development and job status: a critical revision]. / Peso de nacimiento y posterior estado nutricional, desarrollo cognitivo y actividad ocupacional: una revisión crítica.

The impact of prenatal nutritional status, assessed through birth weight (BW) and their effects in the short, medium and long-term on nutritional status, cognitive development and job status in the adult life, has been a problem of interest for several researchers; as regards, some of these report a positive and significant association between these variables and others do not find any relation. Children with insufficient, low or very low BW despite the early more deteriorate nutritional status should present higher risk for brain maturation, failure cognitive development and lowered head circumference which implies both lowered brain volume and intellectual development. In the short and medium-term, this situation damages the learning process at school-age, while in the long-term this might condition the quality of jobs. At present, the body of knowledge pinpoints that findings related to these associations is not conclusive verifying a great controversy in these matters. This review article has the purpose of analyzing the current evidence, in order to stimulate research about to these aspects which are relevant for child development and their future life.

Living donor liver transplantation for unresectable liver metastases from solid pseudo-papillary tumor of the pancreas: a case report.

Solid pseudo-papillary tumors (SPT) are rare primary tumors of the pancreas that primarily affect young women. They are of borderline malignancy, and, unlike other pancreatic malignancies, the prognosis after resection is quite good. However, metastatic disease does occur; the liver is the most common site of tumor dissemination. Herein we have reported a case of a 20-year-old woman who presented with multiple, bilateral liver metastases at 3 years after distal pancreatectomy for SPT of the body and tail of the pancreas. The patient underwent living donor liver transplantation (LDLT) and is alive and disease-free at 24 months after surgery. In this report, we discuss the treatment of liver metastases from SPT, with an emphasis on the possible role of orthotopic liver transplantation (OLT).

Monitoring of fosinopril sodium impurities by liquid chromatography-mass spectrometry including the neural networks in method evaluation.

In this paper, the mass spectrometry (MS) detection has been applied for screening of fosinopril sodium impurities which arise during forced stress study. Before MS analysis, liquid chromatographic method with suitable mobile phase composition was developed. The separation was done on SunFire 100 mm x 4.6 mm 3.5 microm particle size column. The mobile phases which consisted of methanol-ammonium acetate buffer-acetic acid, in different ratios, were used in a preliminary study. Flow rate was 0.3 mL min(-1). Under these conditions, percent of methanol, concentration of ammonium acetate buffer and acetic acid content were tested simultaneously applying central composite design (CCD) and artificial neural network (ANN). The combinations of experimental design (ED) and ANN present powerful technique in method optimization. Input and output variables from CCD were used for network training, verification and testing. Multiple layer perceptron (MLP) with back propagation (BP) algorithm was chosen for network training. When the optimal neural topology was selected, network was trained by adjusting strength of connections between neurons in order to adapt the outputs of whole network to be closer to the desired outputs, or to minimize the sum of the squared errors. From the method optimization the following mobile phase composition was selected as appropriate: methanol-10 mM ammonium acetate buffer-acidic acid (80:19.5:0.5 v/v/v). This mobile phase was used as inlet for MS. According to molecular structure and literature data, electrospray positive ion mode was applied for analysis of fosinopril sodium and its impurities. The proposed method could be used for screening of fosinopril sodium impurities in bulk and pharmaceuticals, as well as for tracking the degradation under stress conditions.

Twelve-year follow-up study of the impact of nutritional status at the onset of elementary school on later educational situation of Chilean school-age children.

OBJECTIVE: To determine the impact of nutritional status in a multicausal approach of socio-economic, socio-cultural, family, intellectual, educational and demographic variables at the onset of elementary school in 1987 on the educational situation of these children in 1998, when they should have graduated from high school. SETTING: Chile's Metropolitan Region. DESIGN: Prospective, observational and 12-year follow-up study. METHODS: A representative sample of 813 elementary first grade school-age children was randomly chosen in 1987. The sample was assessed in two cross-sectional studies. The first cross-sectional study was carried out in at the onset of elementary school in 1987 and the second was carried out in 1998, 12-years later, when they should be graduating from high school. In 1998, 632 adolescent students were located and their educational situation was registered (dropout, delayed, graduated and not located). At the onset of elementary school were determined the nutritional status, socio-economic status (SES), family characteristics, intellectual ability (IA), scholastic achievement (SA) and demographic variables. Statistical analysis included variance tests and Scheffe's test was used for comparison of means. Pearson correlation coefficients and logistic regression were used to establish the most important independent variables at the onset of elementary school in 1987 that affect the educational situation 1998. Data were analysed using the statistical analysis system (SAS). RESULTS: Logistic regression revealed that SES, IA, SA and head circumference-for-age Z score at the onset of elementary school in 1987 were the independent variables with the greatest explanatory power in the educational situation of school-age children in 1998. CONCLUSIONS: These parameters at an early school age are good predictors of the educational situation later and these results can be useful for nutrition and educational planning in early childhood.

Evaluation of impurities level of perindopril tert-butylamine in tablets.

Perindopril tert-butylamine is a new member of angiotensin-converting enzyme inhibitors group used in the treatment of hypertension and heart failure. In this paper, the evaluation of reversed-phase high-performance liquid chromatographic method (RP-HPLC) for the determination of impurities level of perindopril tert-butylamine in tablets was done. The chromatograms were recorded using a Hewlett Packard 1100 chromatographic system with DAD detector. Separations were performed on a YMC-Pack C8 column (250 mm x 4.6mm; 5 microm particle size) at 50 degrees C column temperature. Mobile phase was a mixture of acetonitrile-potassium phosphate buffer (0.05 M) (37:63, v/v) (pH 2.5). pH of the mobile phase was adjusted with ortophosphoric acid. Mixture of acetonitrile-water (40:60, v/v) was used as a solvent. Injection volume was 50 microl, flow rate 1.7 ml min(-1) and UV-detection was performed at 215 nm. The developed method subjected to method validation and parameters in terms of selectivity, linearity, precision, accuracy, limit of detection, limit of quantitation and robustness were defined. The validated method is suitable for the simultaneous determination of perindopril tert-butylamine as well as its impurities in pharmaceuticals.

A health promotion programme in Adventist and non-Adventist women based on Pender's model: a pilot study.

OBJECTIVE: In the last decades, the epidemiological and demographic transition in Chile has resulted in a considerable increase in diet-related non-communicable chronic diseases. The aim of this study was to determine the impact of a health promotion programme (HPP) on behaviour in terms of the dimensions of the health-promoting lifestyle profile (HPLP) based on Pender's model. Pender based his research on the development of a model that explains, predicts and modifies forms of behaviour that promote health; an HPP based on this model may achieve positive changes that promote a healthy lifestyle. STUDY DESIGN: This was a comparative study and the participants were Seventh-Day Adventist Church women (SDAW) and non-Seventh-Day Adventist Church women (NSDAW) aged 20-45 years from the urban area of Villarrica, Ninth Region of Chile. From a population of 300 women (150 SDAW and 150 NSDAW), a random sample of 18 SDAW and 18 NSDAW was chosen. Both groups were comparable in age and socio-economic status. An HPP was undertaken for both groups between April and September 2002. The response rate was 100%. METHODS: The overall score and the scores for the six dimensions of the HPLP (self-actualization, health responsibility, exercise, nutrition, interpersonal support and stress management) were measured in the pre- and post-test periods. Statistical analysis was performed using the Sign test and Wilcoxon's test. Data were processed using the statistical analysis system. RESULTS: In both groups, the median scores increased significantly between the pre- and post-test periods for the overall HPLP score and the scores of the six dimensions. When comparing the median scores in SDAW with NSDAW, only the score for nutrition was significantly higher in SDAW than NSDAW in both the pre-test (P<0.0001) and post-test (P<0.0005) periods. CONCLUSIONS: These findings demonstrate that an HPP based on Pender's model improves behaviour related to a health-promoting lifestyle in both groups, but more so for the NASDW.

Development of liquid chromatographic method for fosinoprilat determination in human plasma using microemulsion as eluent.

Fosinopril sodium presents a prodrug for the active angiotensin converting enzyme (ACE) inhibitor, fosinoprilat. The dual elimination of fosinoprilat by the liver and the kidney distinguishes fosinopril from other angiotensin converting enzyme inhibitors. Such ways of elimination are important for antihypertensive therapy of patients on haemodialysis. The paper presents development and evaluation of a new and sensitive liquid chromatographic (LC) method for the analysis of fosinoprilat in plasma obtained from patients on haemodialysis. A microemulsion system mixture as mobile phase has been used for the separation and analysis of fosinoprilat in plasma samples. The plasma samples were injected directly onto the HPLC system (Waters Breeze) after appropriate sample dilution with mobile phase. Separations were performed on the Bakerbond ENV 4.6 mm x 150 mm, 5 microm particle size column with UV detection at 220 nm. The flow rate was 1.00 mL min(-1). The mobile phase consisted of 1.0% (w/v) of diisopropyl ether, 2.0% (w/v) of sodium dodecyl sulphate (SDS), 6.0% (w/v) of n-propanol and 91% (w/v) of aqueous 25 mM di-sodium hydrogen phosphate, pH adjusted to 2.8 with 85% orthophosphoric acid. The developed method was then subjected to method validation according to the criteria stated in the FDA bioanalytical method validation guidance. The results for specificity, linearity, low limit of quantification (LLOQ), precision, accuracy and stability were within the accepted criteria. The unique approach applied in this paper makes possible the determination of fosinoprilat even in the presence of metabolites of other drugs, so the method can be used for obtaining the reliable results in a fast and simple way.

Development and validation of RP-HPLC method for cetrimonium bromide and lidocaine determination.

The simple and rapid RP-HPLC method, for the simultaneous determination of lidocaine and cetrimonium bromide in the presence of pellet color corrigent, was developed. Separations were performed on a Beckman Ultrasphere ODS 4.6 mm x 15 cm, 5 microm particle column at 40 degrees C. The mobile phase consisted of water phase and acetonitrile (72:28 V/V), pH value of the mobile phase was adjusted to 2.0 with 85% ortophosphoric acid. Bisacodil was used as an internal standard. The flow rate was 1 ml/min and UV detection was performed at 208 nm. The proposed RP-HPLC method was validated and all the parameters for the validation of the method are given. According to the obtained results, the developed method was found to be suitable and accurate for the determination of these drugs in commercial formulations.

Experimental design in reversed-phase high-performance liquid chromatographic analysis of imatinib mesylate and its impurity.

For the determination of the optimal RP-HPLC chromatographic conditions for the separation of imatinib mesylate and its impurity STI 509-00 experimental design 2(4) was applied. All the factors that affect imatinib mesylate/STI 509-00 separation, as well as their mutual interactions were investigated. Methanol and triethylamine content in the mobile phase, pH of the mobile phase and column temperature were independent variables or factors to be investigated in two levels: "low" and "high". Capacity factor was chosen as a dependent variable. From the experimentally determined capacity factor values, it was defined the factors that affect to chromatographic system the most. Applying response surface methodology the appropriate graphs were constructed from experimental points and optimal chromatographic conditions for the separation were defined. Optimal conditions for the separation of imatinib mesylate and STI 509-00 were obtained using X Terra 150 mm x 4.6 mm, particle size 5 microm column at 25 degrees C. Mobile phase consisted of 250 ml of methanol, 740 ml of water and 10 ml of triehylamine. pH of water phase was adjusted to 2.4 with 85% orthophosphoric acid and then methanol was added.

Reversed-phase liquid chromatography analysis of imatinib mesylate and impurity product in Glivec capsules.

The reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for the simultaneous determination of imatinib mesylate and of the impurity product in Glivec capsules (Novartis, Switzerland). Separations were performed on a X Terra 150 mm x 4.6 mm, 5 microm particle size column at 25 degrees C. The mobile phase was a mixture of methanol-water-triethylamine (25:74:1, v/v/v) with flow rate of 1.0 ml min(-1). pH value of water-triethylamine (TEA) was adjusted to 2.4 with orthophosphoric acid before adding of methanol. UV detection was performed at 267 nm. Acetaminophen was used as an internal standard. The method was validated statistically for its selectivity, linearity, precision, accuracy and robustness. Due to its speed and accuracy, the method may be used for quality control analyses.

Optimization of the RP-HPLC method for multicomponent analgetic drug determination.

The optimization of RP-HPLC method defined the simultaneous influence of some important conditions, such as the mobile phase composition, pH of the mobile phase and temperature, on the separation and determination. The RP-HPLC method was done for the determination of paracetamol, caffeine and propyphenazone in a multicomponent pharmaceutical dosage form. The separation factor values define the optimal conditions, which were confirmed by analysing the appropriate mathematical models. The chromatographic system Hewlett Packard 1100 consisted of a HP 1100 pump, HP 1100 UV-VIS detector and HP integrator. Separations were performed on a Beckman Ultrasphere ODS 4.6 x 150 mm, 5 microns particle size column. Samples were introduced through a Rheodyne injector valve with a 20 microL sample loop. UV detection was performed at 265 nm and phenobarottons was used as an internal standard. The optimization was performed within the pH range from 2.5 to 6.0; temperature range from 20 degrees C to 55 degrees C and composition of the mobile phase methanol-water from (30:70 V/V) to (65:35 V/V). The three-D graphs, constructed with sixty-four experimental points, confirmed the optimal conditions for the determination of the investigated analgetic drugs.