RESUMEN
Plasma-free metanephrines and catecholamines are essential markers in the biochemical diagnosis and follow-up of neuroendocrine tumors and inborn errors of metabolism. However, their low circulating concentrations (in the nanomolar range) and poor fragmentation characteristics hinder facile simultaneous quantification by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Here, we present a sensitive and simple matrix derivatization procedure using propionic anhydride that enables simultaneous quantification of unconjugated l-DOPA, catecholamines, and metanephrines in plasma by LC-MS/MS. Dilution of propionic anhydride 1:4 (v/v) in acetonitrile in combination with 50 µL of plasma resulted in the highest mass spectrometric response. In plasma, derivatization resulted in stable derivatives and increased sensitivity by a factor of 4-30 compared with a previous LC-MS/MS method for measuring plasma metanephrines in our laboratory. Furthermore, propionylation increased specificity, especially for 3-methoxytyramine, by preventing interference from antihypertensive medication (ß-blockers). The method was validated according to international guidelines and correlated with a hydrophilic interaction LC-MS/MS method for measuring plasma metanephrines (R2 > 0.99) and high-performance liquid chromatography with an electrochemical detection method for measuring plasma catecholamines (R2 > 0.85). Reference intervals for l-DOPA, catecholamines, and metanephrines in n = 115 healthy individuals were established. Our work shows that analytes in the subnanomolar range in plasma can be derivatized in situ without any preceding sample extraction. The developed method shows improved sensitivity and selectivity over existing methods and enables simultaneous quantification of several classes of amines.
Asunto(s)
Catecolaminas/sangre , Metanefrina/sangre , Espectrometría de Masas en Tándem/métodos , Catecolaminas/aislamiento & purificación , Catecolaminas/normas , Cromatografía Líquida de Alta Presión/normas , Dopamina/análogos & derivados , Dopamina/sangre , Dopamina/aislamiento & purificación , Dopamina/normas , Humanos , Levodopa/sangre , Levodopa/aislamiento & purificación , Levodopa/normas , Límite de Detección , Metanefrina/aislamiento & purificación , Metanefrina/normas , Valores de Referencia , Extracción en Fase Sólida , Espectrometría de Masas en Tándem/normasRESUMEN
BACKGROUND: Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca2+ sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock. METHODS: Relevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed. RESULTS: A total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% (n = 1 of 30), followed by EP 3.11% (n = 5 of 161), and then VP 3.10% (n = 19 of 613), NE 3.03% (n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% (n = 4 of 199), LE 1.16% (n = 3 of 258), and PA 0.39% (n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% (n = 258 of 992), followed by EP 22.98% (n = 37 of 161), and then NE/DB 20.60% (n = 41 of 199), NE/EP 20.0% (n = 6 of 30), NE 8.33% (n = 127 of 1525), LE 5.81% (n = 15 of 258), PA 2.33% (n = 6 of 257), and VP 1.67% (n = 10 of 600). CONCLUSIONS: The use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output.
Asunto(s)
Catecolaminas/normas , Choque Séptico/tratamiento farmacológico , Catecolaminas/uso terapéutico , Dopamina/normas , Dopamina/uso terapéutico , Humanos , Mortalidad/tendencias , Norepinefrina/normas , Norepinefrina/uso terapéutico , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Terlipresina/normas , Terlipresina/uso terapéutico , Vasopresinas/normas , Vasopresinas/uso terapéuticoRESUMEN
In vivo electrochemistry is one powerful strategy for probing brain chemistry. However, the decreases in sensitivity mainly caused by the adsorption of proteins onto electrode surface in short-term in vivo measurements unfortunately render great challenges in both electrode calibration and selectivity against the alternation of proteins. In this study, we observe that the pretreatment of carbon fiber microelectrodes (CFEs) with bovine serum albumin (BSA) would offer a simple but effective strategy to the challenges mentioned above. We verify our strategy for dopamine (DA) with conventionally used CFEs and for ascorbate with our previously developed carbon nanotube-modified CFEs. We find that, in artificial cerebral spinal fluid (aCSF) solution containing BSA, the current responses of the microelectrodes equilibrate shortly and the results for precalibration carried out in this solution are found to be almost the same as those for the postcalibration in pure aCSF. This observation offers a new solution to electrode calibration for in vivo measurements with a technical simplicity. Furthermore, we find that the use of BSA pretreated CFEs to replace bare CFEs would minimize the interference from the alternation of proteins in the brain. This study offers a new general and effective approach to in vivo electrochemistry with a high reliability and a simplified procedure.
Asunto(s)
Dopamina/análisis , Técnicas Electroquímicas , Albúmina Sérica Bovina/química , Animales , Ácido Ascórbico/análisis , Encéfalo/metabolismo , Calibración , Carbono/química , Fibra de Carbono , Dopamina/normas , Técnicas Electroquímicas/normas , Electrodos Implantados , Masculino , Microelectrodos , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: In this study, we developed and validated a HPLC-MS/MS method capable of simultaneously determining levodopa, carbidopa, entacapone, tolcapone, 3-O-methyldopa and dopamine in human plasma. RESULTS & METHODOLOGY: Chromatographic separation was achieved using a C8 column with a mobile phase consisting of a gradient of water and acetonitrile:methanol (90:10 v/v), both containing 0.1% formic acid. The developed method was selective, sensitive (LD<7.0 ng ml(-1)), linear (r>0.99), precise (RSD<11.3%), accurate (RE<11.8%) and free of residual and matrix effects. The developed method was successfully applied in plasma patients with Parkinson's disease using Stalevo®. CONCLUSION: The new method can be used for the clinical monitoring of these substances and applied to adjustments in drug dosages.
Asunto(s)
Benzofenonas/sangre , Análisis Químico de la Sangre/métodos , Carbidopa/sangre , Catecoles/sangre , Cromatografía Líquida de Alta Presión , Dihidroxifenilalanina/análogos & derivados , Dopamina/sangre , Levodopa/sangre , Nitrilos/sangre , Nitrofenoles/sangre , Espectrometría de Masas en Tándem , Benzofenonas/normas , Carbidopa/normas , Catecoles/normas , Cromatografía Líquida de Alta Presión/normas , Dihidroxifenilalanina/sangre , Dihidroxifenilalanina/normas , Dopamina/normas , Humanos , Levodopa/normas , Nitrilos/normas , Nitrofenoles/normas , Control de Calidad , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/normas , Tolcapona , Tirosina/análogos & derivadosRESUMEN
Fast-scan cyclic voltammetry (FSCV) is a common analytical electrochemistry tool used to measure chemical species. It has recently been adapted for measurement of neurotransmitters such as dopamine in awake and behaving animals (in vivo). Electrode calibration is an essential step in FSCV to relate observed current to concentration of a chemical species. However, existing methods require multiple components, which reduce the ease of calibrations. To this end, a microfluidic flow cell (µFC) was developed as a simple device to switch between buffer and buffer with a known concentration of the analyte of interest--in this case dopamine--in a microfluidic Y-channel. The ability to quickly switch solutions yielded electrode calibrations with faster rise times and that were more stable at peak current values. The µFC reduced the number of external electrical components and produced linear calibrations over a range of concentrations. To demonstrate this, an electrode calibrated with the µFC was used in FSCV recordings from a rat during the delivery of food reward--a stimulus that reliably evokes a brief increase in current due to the oxidation of dopamine. Using the linear calibration, dopamine concentrations were determined from the current responses evoked during the behavioral task. The µFC is able to easily and quickly calibrate FSCV electrode responses to chemical species for both in vitro and in vivo experiments.
Asunto(s)
Técnicas Electroquímicas , Técnicas Analíticas Microfluídicas/instrumentación , Animales , Calibración , Dopamina/análisis , Dopamina/normas , Técnicas Electroquímicas/normas , Electrodos , Concentración de Iones de Hidrógeno , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
A novel chemiluminescence system coupled with a reverse flow injection analysis for the determination of dopamine hydrochloride was presented. It is based on th e strong quench effect of dopamine hydrochloride on the chemiluminescence reaction between luminol and hexacyanoferrate(III) under alkaline condition. Various factors affecting the chemiluminescence intensity of the system were investigated. The possible mechanism of the proposed method was also studied. The decrease of chemiluminescence intensity was linear with the dopamine hydrochloride content in the range of 2.0 x 10(-9) -8.0 x 10(-7) g x mL(-1), the detection limit of the method was 1.14 x 10(-9) g x mL(-1), and the relative standard deviation was 0.99% (4.0 x 10(-7) g x mL(-1), n = 11). It was successfully used for the determination of the content of dopamine hydrochloride in dopamine hydrochloride injection.
Asunto(s)
Dopamina/análisis , Ferrocianuros/química , Mediciones Luminiscentes/métodos , Luminol/química , Dopamina/química , Dopamina/normas , Análisis de Inyección de Flujo , Concentración de Iones de Hidrógeno , Hidróxidos/química , Luminiscencia , Mediciones Luminiscentes/instrumentación , Compuestos de Potasio/química , Estándares de Referencia , Reproducibilidad de los Resultados , Espectrometría de Fluorescencia/instrumentación , Espectrometría de Fluorescencia/métodosRESUMEN
A novel flow-injection method (FIA) for the determination of dopamine based on the inhibition of the intensity of chemiluminescence (CL) from luminol-hexacyanoferrate(III) system in basic medium is described. The present method allows the determination of dopamine over the range 30-100 microg l(-1) and 400-3000 microg l(-1). The relative standard deviation is 2.32% for 70 microg l(-1) dopamine and 1.22% for 1500 microg l(-1) dopamine (n = 20). The detection limit is 5 microg l(-1) with the sampling rate of 135 samples h(-1). This method has been applied for the determination of dopamine in commercial pharmaceutical injection samples. The results obtained by this method agreed with those by the official method.