Therapeutic Drug Monitoring in Oncohematological Patients: A Fast and Accurate HPLC-UV Method for the Quantification of Nilotinib in Human Plasma and Its Clinical Application.

Nilotinib, a second-generation tyrosine kinase inhibitor, has demonstrated clinical activity in chronic myeloid leukemia. As an exposure-response relationship has been observed for nilotinib, its therapeutic drug monitoring could be a valuable tool in clinical practice. Therefore, the aim of this study was to develop and validate a selective and precise high performance liquid chromatography-ultraviolet method for the measurement of nilotinib in plasma from patients with cancer. After protein precipitation extraction with acetonitrile, nilotinib and rilpivirine were separated using isocratic elution on a Tracer Excel 120 ODS C18 column using a mobile phase consisting of a mixture of potassium dihydrogen phosphate-buffered solution (pH 5.5; 0.037 M)-methanol-acetonitrile (45:45:10, v/v/v), pumped at a flow rate of 1.7 mL·min-1. A wavelength of 254 nm was selected for the quantification of the analyte and the internal standard (IS). The technique was validated following the guidelines for the validation of analytical methods of regulatory agencies (Food and Drug Administration (FDA) and the European Medicines Agency (EMA)). Linearity was established in a concentration range between 125 and 7000 ng/mL. The detection limit was 90 ng/mL, and the lower limit of quantification was 125 ng/mL. For all concentrations in the calibration curve, the intraday and interday coefficients of variation were less than 4.1%. Median recovery of nilotinib from plasma was ≥65.1% (±21.4%). The method described is sensitive, selective, reproducible, and rapid, and can be used for the accurate determination of nilotinib in human plasma for pharmacokinetics studies and for therapeutic drug monitoring (TDM) of nilotinib in routine clinical practice.

Low-Cost Electronic Nose for the Determination of Urinary Infections.

Currently, urine samples for bacterial or fungal infections require a long diagnostic period (48 h). In the present work, a point-of-care device known as an electronic nose (eNose) has been designed based on the "smell print" of infections, since each one emits various volatile organic compounds (VOC) that can be registered by the electronic systems of the device and recognized in a very short time. Urine samples were analyzed in parallel using urine culture and eNose technology. A total of 203 urine samples were analyzed, of which 106 were infected and 97 were not infected. A principal component analysis (PCA) was performed using these data. The algorithm was initially capable of correctly classifying 49% of the total samples. By using SVM-based models, it is possible to improve the accuracy of the classification up to 74% when randomly using 85% of the data for training and 15% for validation. The model is evaluated as having a correct classification rate of 74%. In conclusion, the diagnostic accuracy of the eNose in urine samples is high, promising and amenable for further improvement, and the eNose has the potential to become a feasible, reproducible, low-cost and high-precision device to be applied in clinical practice for the diagnosis of urinary tract infections.

Evaluación clínica de un nuevo método molecular para la detección de microorganismos multirresistentes / Clinical evaluation of a new molecular method for the detection of multidrug-resistant microorganisms

Introducción: El objetivo fue realizar la validación clínica del sistema molecular AMR Direct Flow Chip® para la detección de genes de resistencia a antimicrobianos partiendo de aislados bacterianos en cultivo, así como de hisopos de muestras nasales o rectales. Métodos: El ensayo AMR es una PCR multiplex seguida de hibridación reversa tipo dot blot en arrays de ADN completamente automatizada mediante la plataforma HS24, con un tiempo de realización de 3h. Se realizó la validación preclínica con 104 cepas bacterianas caracterizadas y posteriormente se analizaron 210 muestras de hisopos nasales o rectales. Resultados: La sensibilidad y la especificidad del ensayo preclínico fueron del 100%, identificando correctamente las 104 cepas. En la validación clínica, la sensibilidad fue del 100% y la especificidad fue del 100% en muestras rectales y del 97% en hisopos nasales. Conclusiones: El sistema AMR Direct Flow Chip® es un sistema rápido y eficaz para la detección de microorganismos multirresistentes a partir de muestras rectales y nasales.(AU)

Introduction The main objective of this work is to carry out the clinical validation of the trial with the AMR Direct Flow Chip® starting from either nasal swabs, rectal swabs directly or from isolated strains to detect antibiotic resistance genes. Methods: We developed the preclinical validation of the assay with 104 known bacterial isolates. A total of 210 nasal or rectal swab samples were analyzed. The AMR assay is based on multiplex PCR followed by reverse dot blot hybridization on DNA arrays fully automated by using the HS24 platform. The completion time of the full analysis is 3 hours. Results :Both the sensitivity and specificity of the preclinical assay were 100%, with the 104 samples correctly identified. In the clinical validation, the sensitivity was 100% and the specificity was between 100% in rectal swabs and 97% in nasal swabs. Conclusions: The AMR Direct Flow Chip® is a rapid and effective assay for the detection of multidrug-resistant microorganisms from nasal and rectal swab samples.(AU)

Clinical evaluation of a new molecular method for the detection of multidrug-resistant microorganisms.

INTRODUCTION: The main objective of this work is to carry out the clinical validation of the trial with the AMR Direct Flow Chip starting from either nasal swabs, rectal swabs directly or from isolated strains to detect antibiotic resistance genes. METHODS: We developed the preclinical validation of the assay with 104 known bacterial isolates. A total of 210 nasal or rectal swab samples were analyzed. The AMR assay is based on multiplex PCR followed by reverse dot blot hybridization on DNA arrays fully automated by using the HS24 platform. RESULTS: Both the sensitivity and specificity of the preclinical assay were 100%, with the 104 samples correctly identified. In the clinical validation, the sensitivity was 100% and the specificity was between 100% in nasal swabs and 97% in rectal swabs. CONCLUSIONS: The AMR Direct Flow Chip® is a rapid and effective assay for the detection of multidrug-resistant microorganisms (MDR) from nasal and rectal swab samples.

Theory of Mind in Borderline Personality Disorder: A Possible Endophenotypic Factor?

The purpose of this study is to examine whether theory of mind (ToM) is an endophenotypic marker of borderline personality disorder (BPD), thus constituting an etiopathogenic factor of the disease. This would suggest familial vulnerability to BPD. This was a case-control study involving 146 individuals with 57 BPD patients, 32 first-degree relatives, and 57 controls (median age of BPD and control = 33.4 years; relatives = 52.9 years; BPD females and controls = 91.2%; female relatives = 62.5%). All the participants completed the Spanish version of the Movie for the Assessment of Social Cognition test to evaluate the ToM subclassification: interpretation of emotions, thoughts and intentions. BPD patients and their healthy first-degree relatives exhibited significant deficits in the correct interpretation of emotions and intentions compared to healthy controls. Both patients with BPD and their healthy first-degree relatives exhibited significant deficits in ToM, which suggests that it may be an etiopathogenic factor of BPD, and ToM (interpretation of emotions, thoughts and intentions) is a possible endophenotypic marker of BPD, suggesting a genetic predisposition to the disorder. Therefore, ToM could be considered as an indicator for the early detection of the disorder of and intervention for BPD.

Clinical evaluation of a new molecular method for the detection of multidrug-resistant microorganisms. / Evaluación clínica de un nuevo método molecular para la detección de microorganismos multirresistentes.

INTRODUCTION: The main objective of this work is to carry out the clinical validation of the trial with the AMR Direct Flow Chip® starting from either nasal swabs, rectal swabs directly or from isolated strains to detect antibiotic resistance genes. METHODS: We developed the preclinical validation of the assay with 104 known bacterial isolates. A total of 210 nasal or rectal swab samples were analyzed. The AMR assay is based on multiplex PCR followed by reverse dot blot hybridization on DNA arrays fully automated by using the HS24 platform. The completion time of the full analysis is 3 hours. RESULTS: Both the sensitivity and specificity of the preclinical assay were 100%, with the 104 samples correctly identified. In the clinical validation, the sensitivity was 100% and the specificity was between 100% in rectal swabs and 97% in nasal swabs. CONCLUSIONS: The AMR Direct Flow Chip® is a rapid and effective assay for the detection of multidrug-resistant microorganisms from nasal and rectal swab samples.

Social cognition and social functioning in people with borderline personality disorder and their first-degree relatives.

BACKGROUND: A few papers studying healthy, first-degree relatives of people with borderline personality disorder (BPD) have found that this group presents attention and memory problems. However, current research has not analyzed their social cognition. MATERIALS AND METHODS: We designed an age-, gender- and education-level matched case-control study involving 57 people with BPD, 32 of their first-degree relatives, and 57 healthy controls in Spain in 2018-2019. All were assessed for social cognition and functioning using the Movie for Assessment of Social Cognition and the Social Functioning Scale; other potential confounders were also collected (marital status, occupation and household variables). RESULTS: There were differences in the social cognition domain of overmentalizing errors, with the BPD group scoring significantly higher than controls; however, there was no significant difference with relatives; in the social functioning domain of family relationships, with the controls showing the highest scores. Social engagement/withdrawal, interpersonal behavior, independence-competence, prosocial activities, full scale and categorization domains showed the same pattern: the BPD group had lower scores than their relatives and the controls. Relatives were significantly different from BPD patients in family relationships, social engagement/withdrawal and interpersonal behavior, as well as on the full Social Functioning Scale (both as a linear and categorical variable). However, only controls showed differences with relatives in family relationships. CONCLUSIONS: All in all, relatives show similar levels of social cognition and functioning compared with controls, and people with BPD show some alterations in different domains of both social cognition and functioning.

Midazolam and haloperidol for palliative sedation: physicochemical stability and compatibility of parenteral admixtures

This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.

Stability and compatibility of ondansetron with haloperidol in parenteral admixtures.

BACKGROUND: The chemical stability of coadministered ondansetron (OND) and haloperidol (HAL) in parenteral admixtures has not been described yet. OBJECTIVE: The aim of the present work is to study the chemical stability and the compatibility of OND and HAL admixtures. METHODS: Normal saline solution and dextrose were used to prepare the admixture solutions of the drugs; the materials of the containers were the original plastic bags of the diluents and the stability was studied at 20°C. Compatibility was studied by visual inspection of no colour change and turbidity or precipitation appearance. The concentration of the drugs was studied by ultraviolet detection high-performance liquid chromatography. The method was validated following the Food and Drug Administration and European Medicines Agency guidelines, and the assay enables the measurement of both drugs with a linear calibration curve (r=0.999) over the concentration range 10-100 µg/mL, with acceptable values of linearity, precision and accuracy. Darunavir was used as internal standard. RESULTS: Most of the admixtures have an adequate concentration until 24 hours(less than 10% of loss). 25% of the samples show a higher loss at 24 hours, and the chemical stability of these samples is 12 hours. CONCLUSIONS: The stability and compatibility of OND and HAL in the coadministered admixtures in Viaflo plastic bags with normal saline or dextrose are suggested at 12 hours.

Chemical stability of ondansetron hydrochloride with other drugs in admixtures via parenteral; a review / Revisión de la estabilidad química del ondansetrón con otros medicamentos en mezclas de administración parenteral

Objective: This review was prepared to offer the most complete information about the use of ondansetron in parenteral admixtures with other drugs. Method: The search was done from September 2016 to April 2017 by using electronic databases Stabilis® and Micromedex® solutions, Medline/PubMed and Scholar Google searching publications about ondansetron stability in parenteral infusion when is administered by itself or with other medication. Results: 49 studies are included with a total of 53 drugs. 15 drugs were found compatible administered with ondansetron in a clinical routine concentration range in intravenous administration. Also, four ternary blends were found compatible and another one was incompatible. Otherwise, 38 drugs were found incompatible. Conclusions: Compatibility of ondansetron offers a broad number of options to be used to avoid nausea and vomiting symptoms in patients with other concomitant medication (AU)

Objetivo: Esta revisión ha sido preparada para recopilar toda la información referente a la estabilidad del ondansetrón en mezclas parenterales junto a otros fármacos. Método: La búsqueda fue realizada entre septiembre de 2016 y abril de 2017 empleando bases de datos electrónicas como Stabilis® y Micromedex® solutions, Medline/PubMed y Google Académico buscando publicaciones sobre la estabilidad del ondansetrón para infusión vía parenteral cuando es administrado en monoterapia o en una mezcla con otros fármacos. Resultados: En este trabajo han sido incluidos 49 artículos con un total de 53 fármacos. 15 fármacos han sido descritos como compatibles con ondansetrón en concentraciones habituales en la clínica práctica para administración intravenosa. Además, cuatro mezclas ternarias han sido descritas como compatibles y una como incompatible. Por otro lado, 38 fármacos han sido descritos como incompatibles para su administración con ondansetrón. Conclusiones: La compatibilidad del ondansetrón ofrece un amplio rango de opciones para evitar los síntomas de náuseas y vómitos en pacientes con otra medicación concomitante (AU)

Chemical stability of ondansetron hydrochloride with other drugs in admixtures via parenteral; a review.

OBJECTIVE: This review was prepared to offer the most complete information about the use of ondansetron in parenteral admixtures with other drugs. METHOD: The search was done from September 2016 to April 2017 by using electronic databases Stabilis® and Micromedex® solutions, Medline/PubMed and Scholar Google searching publications about ondansetron stability in parenteral infusion when is administered by itself or with other medication. RESULTS: 49 studies are included with a total of 53 drugs. 15 drugs were found compatible administered with ondansetron in a clinical routine concentration range in intravenous administration. Also, four ternary blends were found compatible and another one was incompatible. Otherwise, 38 drugs were found incompatible. DISCUSSION: Compatibility of ondansetron offers a broad number of options to be used to avoid nausea and vomiting symptoms in patients with other concomitant medication.

Objetivo: Esta revisión ha sido preparada para recopilar toda la información referente a la estabilidad del ondansetrón en mezclas parenterales junto a otros fármacos.Método: La búsqueda fue realizada entre septiembre de 2016 y abril de 2017 empleando bases de datos electrónicas como Stabilis® y Micromedex® solutions, Medline/PubMed y Google Académico buscando publicaciones sobre la estabilidad del ondansetrón para infusión vía parenteral cuando es administrado en monoterapia o en una mezcla con otros fármacos.Resultados: En este trabajo han sido incluidos 49 artículos con un total de 53 fármacos. 15 fármacos han sido descritos como compatibles con ondansetrón en concentraciones habituales en la clínica práctica para administración intravenosa. Además, cuatro mezclas ternarias han sido descritas como compatibles y una como incompatible. Por otro lado, 38 fármacos han sido descritos como incompatibles para su administración con ondansetrón.Discusión: La compatibilidad del ondansetrón ofrece un amplio rango de opciones para evitar los síntomas de náuseas y vómitos en pacientes con otra medicación concomitante.

A rapid validated UV-HPLC method for the simultaneous determination of the antiretroviral compounds darunavir and raltegravir in their dosage form / Determinación simultánea de los compuestos antirretrovirales darunavir y raltegravir en su forma farmacéutica mediante un método rápido y validado de UV-HPLC

Introduction. A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet detection has been developed for quantification of darunavir and raltegravir in their pharmaceutical dosage form. Material and methods. The assay enables the measurement of both drugs with a linear calibration curve (R2= 0.999) over the concentration range 5-100 mg/L. The determination was performed on an analytical Tracer Excel 120 ODSB (15x0.4.6 cm) column at 35ºC. The selected wavelength was 254 nm. The mobile phase was a mixture of 0.037 M sodium dihydrogen phosphate buffer, acetonitrile and methanol (40:50:10, v/v/v) at a flow rate of 2.0 mL/min Nevirapine (50 mg/L) was used as internal standard. Results. Accuracy, intraday repeatability (n = 5), and inter-day precision (n = 3) were found to be satisfactory, being the accuracy from -4.33 to 3.88% and precisions were intra-day and interday, 0.25% and 4.42% respectively in case of darunavir. Raltegravir intraday and interday precisions lower of 1.01 and 2.36%, respectively and accuracy values bet from -4.02 to 1.06%. Conclusions. Determination of the darunavir and raltegravir in their dosage form was done with a maximum deviation of 4%. This analytical method is rapid, easily implantable and offers good results (AU)

Introducción. Un método rápido, sencillo y sensible de cromatografía líquida de alto rendimiento (HPLC) con detección ultravioleta ha sido desarrollado para la cuantificación simultánea de darunavir y raltegravir en su forma farmacéutica. Material y métodos. La determinación se llevó a cabo empleando una columna Tracer Excel 120 ODSB (15x0.4.6 cm) C18 a 35 ºC. La longitud de onda empleada fue de 254 nm. La fase móvil fue una mezcla de una disolución tampón dihidrógeno fosfato de sodio 0,037 M, acetonitrilo y metanol (40:50:10, v/v/v) con un flujo de 2,0 mL/min. El fármaco nevirapina (50 mg/L) fue usado como patrón interno. Resultados. El ensayo realiza la medida de ambos fármacos con una curva de calibración lineal (R2= 0,999) en un rango de concentración de 5 a 100 mg/L. Los valores de exactitud, repetibilidad intradía (n = 5) e interdía (n = 3) han resultado satisfactorios, encontrándose los valores de exactitud entre -4.33 y 3.88%, y las precisiones intradía e interdía, 0,25% y 4,42%, respectivamente en caso de darunavir. En el caso del raltegravir, las precisiones intradía e interdía fueron de 1,01 y 2,36%, respectivamente y para la exactitud se obtuvieron valores entre -4,02 y 1,06%. Conclusiones. La determinación de darunavir y raltegravir en su forma farmacéutica fue llevada a cabo observándose una desviación máxima del 4%. El método es rápido, fácilmente implantable y ofrece buenos resultados (AU)