A sensitive and fast ultra performance liquid chromatography‐electrospray ionization‐tandem mass spectrometry (UPLC‐ESI‐MS/MS) method for measurements of N‐butylscopolamine in plasma was developed and validated. A single protein precipitation was proposed for the clean up of the plasma and N‐methylhomatropine was added as internal standard (IS). The analyses were carried out using a C18 column and mobile phase of acetonitrile: 5 mM ammonium acetate + 0.1% formic acid (90:10, v/v). The triple quadrupole mass spectrometer equipped with an electrospray source in positive mode, was set up in selective reaction monitoring, to detect precursor → product ion 360.0 → 194.0 m/z and 290.3 → 138.0 m/z transitions, for N‐butylscopolamine and IS, respectively. The method was linear in 0.03 (lower limit of quantitation; LLOQ) – 10.00 ng/ml range for N‐butylscopolamine. Satisfactory selectivity, linearity, precision, accuracy, and robustness were obtained for the UPLC‐ESI‐MS/MS method. The proposed method was successfully applied to a pharmacokinetic study of healthy human volunteers; the results showed that the two scopolamine butylbromide formulations tested are not bioequivalent in rate and extent of absorption. Copyright © 2012 John Wiley & Sons, Ltd.

This study was to evaluate and compare the pharmacokinetic and pharmacodynamic behavior of two formulations of furosemide (CAS 54-31-9) 40 mg tablets, administered as a single dose to healthy subjects. Plasma concentrations of furosemide were determined with a validated method by liquid chromatography coupled to mass spectrometry (LC-MS/MS). We obtained the parameters: AUC 0-t , AUC 0-∞ , K el , T 1/2 , C max e T max. The following parameters were determined in urine: Sodium, Potassium and Chlorine and the total volume. The 90% confidence intervals for the ratio of C max (93.63-121.92%), AUC 0-t (96.80-115.72%) and AUC 0-∞ (98.45-117.43%) respectively for test and reference. Statistical analysis of the similarity of the parameters for urinary volume, excretion of sodium, potassium and chlorine and assuming that both formulations reach the same plasma levels, we expect that the pharmacological effect is also the same. Whereas the rate and extent of absorption, both products can be considered therapeutic equivalents.

A sensitive and specific LC/MS/MS method was developed and validated for the determination of scopolamine butylbromide in human plasma. Scopolamine butylbromide and propanolol (internal standard) were extracted from the plasma by liquidliquid extraction with dichloromethane as the extraction solvent and separated on a C18 analytical column (50 4.6 mm id) maintained at 40C. The analytes were eluted at a constant flow rate of 0.45 mL/min; the mobile phase consisted of acetonitrile and a buffer of 5 mM ammonium acetate and 0.1 formic acid (60 + 40, v/v). The mass spectrometer, equipped with an electrospray source in the positive ionization mode, was set up in the multiple-reaction monitoring mode to monitor the transitions m/z 360.6 > 102.5 (scopolamine butylbromide) and m/z 259.7 > 115.6 (propanolol). The chromatographic separation was obtained within 2.0 min, and the responses were linear over the concentration range of 0.1040.00 ng/mL. The mean extraction recoveries of scopolamine butylbromide and propanolol from plasma were 69.00 and 80.76, respectively. Method validation parameters, such as specificity, linearity, precision, accuracy, and stability, were within the acceptable range. Moreover, when the proposed method was successfully applied to a pharmacokinetic study of healthy human volunteers, the results showed that the two scopolamine butylbromide formulations tested are not bioequivalent in rate and extent of absorption.

Secnidazole is an antimicrobial agent used primarily in the treatment of amoebiasis. For this bioequivalence study of secnidazole, twenty-eight healthy female volunteers were enrolled in a randomized crossover study. Each volunteer was given a single oral dose of secnidazole test preparation and then the reference preparation, or vice versa, with a wash out interval of two weeks. The plasma concentrations of secnidazole were determined by HPLC, and the samples were extracted with tert-butyl-methyl-ether: dicloromethane (60:40, v/v). Secnidazole and its parent compound metronidazole were separated on a C18 column with water:acetonitrile (85:15, v/v) as the mobile phase, and monitored at 310 nm. The ratio of mean C max , AUC 0−t and AUC 0−∞ values for the test and reference products were within the predetermined range established by ANVISA, demonstrating that the two formulations are bioequivalent in rate and extent of absorption. Uniterms:Oral formulas/bioequivalence study. Secnidazole/bioavailability. Antimicrobials/ bioavailability. Secnidazol é um agente antimicrobiano utilizado principalmente no tratamento da amebíase. Para este estudo de bioequivalência de secnidazol em voluntários saudáveis, foram incluídos vinte e oito voluntárias mulheres no estudo randomizado cruzado. Cada voluntária recebeu uma única dose oral de secnidazol do produto teste e referência para comparação, com um intervalo de wash-out de duas semanas. As concentrações plasmáticas de secnidazol foram determinados por CLAE, as amostras foram extraídas com terc -butil-metil-éter: dicloromethano (60:40, v/v). O secnidazol e seu padrão interno metronidazol foram separados em uma coluna (C18 ) com fase móvel água ultra-pura:acetonitrila (85:15, v/v) e monitorado em 310 nm. As razões entre as médias geométricas de C máx , ASC 0-t e ASC 0-∞ , encontraramse dentro do estabelecido pela ANVISA, demonstrando que as formulações são bioequivalentes quanto à taxa e extensão de absorção Unitermos: Formulações orais/estudo de bioequivalência. Secnidazol/biodisponibilidade. Antimicrobianos/biodisponibilidade.

Plasma monitoring and pharmacokinetic assessment are important tools used in therapeutic control. Sufentanil is responsible for the hemodynamic stabilization of patients, providing better suppression of the neuroendocrine response compared to its analogue fentanyl. This study aims to use the plasma monitoring of sufentanil in patients undergoing cardiac surgery with extracorporeal circulation (ECC, group 1) or without ECC (group 2) to assess the pharmacokinetics of the compound.The 42 patients in this study received 0.5 μg/kg of sufentanil through bolus injection followed by a maintenance infusion of 0.5 μg/kg.h. Serial blood samples were collected during the post induction intraoperative period and during the postoperative period until 36 h after sufentanil administration. The plasma concentrations were determined by a validated method utilizing liquid chromatography coupled to mass spectrometry. The pharmacokinetic modeling was performed using a 3-compartment model fit.The surgical patients included in the protocol were adults of both genders, with 30 patients in the ECC group and 12 in the group without ECC. The plasma concentrations obtained were significantly different between the 2 groups. During the extracorporeal circulation procedure, intense fluctuations were observed in the sufentanil plasma concentrations. Compared with the results of group 2, the ECC procedure reduced the terminal or gamma half-life from 36.35 ± 6.37 h to 23.25 ± 2.75 h in group 1. In addition, the ECC procedure promoted higher fluctuations in the sufentanil plasma concentrations without causing alterations in the area under the curve, distribution volume, clearance or the distributional (alpha) and rapid elimination (beta) half-lives (t1/2α and t1/2β, respectively).

Objetivo: validar um instrumento para avaliar as competências de letramento funcional em saúde para familiares de crianças e verificar sua associação com características sociodemográficas. Metodologia: Estudo metodológico, com 302 familiares de crianças até um ano de idade que participaram da validação clínica do instrumento em sua versão brasileira, em unidades de atenção primária de município do Oeste do Paraná, em 2019 e 2020. Realizou-se análise estatística descritiva e inferencial. Resultados: A confiabilidade interna do teste, medida pelo método de Kuder-Richardson foi substancial (KR-20 = 0,70) e manteve-se na análise fatorial confirmatória uma dimensão, como no original. O letramento funcional em saúde foi definido pela mediana das respostas, obtendo-se 70 como ponto de corte. Obtiveram letramento funcional em saúde satisfatório 67,4% dos participantes. Dentre os familiares predominaram as mães (93.4%), a idade média dos participantes foi 28,3 anos, 53,6% completaram o ensino médio, a renda prevalente foi até dois salários-mínimos e 55,3% utilizavam exclusivamente a unidade de atenção primária para assistência à saúde da criança. Na correlação entre características sociodemográficas e letramento funcional em saúde, maior renda e mais anos de escolaridade influenciaram em melhores resultados de letramento. Conclusão: O estudo contribui com um instrumento confiável de verificação do letramento funcional em saúde para o cuidado de crianças, inédito no Brasil.

A fast, sensitive, and specific liquid chromatographic/tandem mass spectrometric method was developed and validated for determination of tetracycline in human plasma. Tetracycline and oxytetracycline [internal standard (IS)] were extracted from the plasma by protein precipitation. The mobile phase consisted of acetonitrileformic acid 0.1 (48 + 52, v/v), run at a flow rate of 1 mL/min (split 1:5). Detection was performed by positive electrospray ionization in multiple reaction monitoring mode, monitoring the transitions 444.8 > 410.0 and 461.0 > 426.0 for tetracycline and IS, respectively. The analysis was performed in 3.5 min and the method was linear in the plasma concentration range of 506000 ng/mL. The mean extraction recoveries for tetracycline and IS from plasma were 92.14 and 94.04, respectively. Method validation investigated parameters such as the linearity, precision, accuracy, specificity, and stability, giving results within the acceptable range. The proposed method was successfully applied for determination of tetracycline in human plasma samples to support bioequivalence studies.

An analytical method based on reversed phase liquid chromatography (RP-LC) was developed and validated for the determination of acyclovir in human plasma. Acyclovir and guanine (internal standard) were extracted from the plasma by liquid-liquid extraction using acidified acetonitrile as extraction solvent, and separated on a C 18 analytical column (150'mm  4.6 mm I.D.) maintained at 308C. The elution was performed by a fast gradient at a constant flow rate of 1.0 mL/min and the mobile phase A consisted of 1% formic acid, and mobile phase B consisted of acetonitrile. The fluorescence detector was set at 270 nm (excitation) and 380 nm (emission). The chromatographic separation was obtained within 16.0 min and was linear in the concentration range of 20 -3000 ng/mL. The mean extraction recoveries of acyclovir and guanine from plasma were 82.2 and 76.0%, respectively. Method validation investigated parameters such as the specificity, linearity, precision, accuracy, and stability, giving results within the acceptable range. Moreover, the proposed method was successfully applied to a pharmacokinetic study in healthy human volunteers, and results showed that the two acyclovir formulations are bioequivalent in their rate and extent of absorption.