scholarly journals Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110331
Author(s):  
Radamés Alemón-Medina ◽  
Nelly Altamirano-Bustamante ◽  
Gustavo Lugo-Goytia ◽  
Raquel García-Álvarez ◽  
Liliana Rivera-Espinosa ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Clinical Trial ◽  
Dose Adjustment ◽  
Geometric Mean ◽  
Tandem Mass ◽  
Liquid Formulation ◽  
Blood Samples ◽  
Direct Precipitation ◽  
Comparative Bioavailability ◽  
Solid Form

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: Cmax 1503.2 ng/mL vs 1521.4, Tmax 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13–113.6), 98.08% (88.04–109.2), and 97.52% (84.9–112.01), for Cmax, AUC0-t, and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

scholarly journals Simultaneous Determination of Cyclosporine A, Tacrolimus, Sirolimus, and Everolimus in Whole-Blood Samples by LC-MS/MS

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Mustafa Karapirli ◽  
Murat Kizilgun ◽  
Ozgur Yesilyurt ◽  
Husamettin Gul ◽  
Zeki Ilker Kunak ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Simultaneous Determination ◽  
Cyclosporine A ◽  
Whole Blood ◽  
Immunosuppressive Drugs ◽  
Tandem Mass ◽  
Blood Samples ◽  
Whole Blood Samples

Objectives. Cyclosporine A (CyA), tacrolimus (TRL), sirolimus (SIR), and everolimus (RAD) are immunosuppressive drugs frequently used in organ transplantation. Our aim was to confirm a robust sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of CyA, TRL, SIR, and RAD in whole-blood samples.Materials and Methods. We used an integrated online solid-phase extraction-LC-MS/MS system and atmospheric pressure ionization tandem mass spectrometry (API-MS/MS) in the multiple reaction monitoring (MRM) detection mode. CyA, TRL, SIR, and RAD were simultaneously analyzed in whole blood treated with precipitation reagent taken from transplant patients.Results. System performance parameters were suitable for using this method as a high-throughput technique in clinical practice. The high concentration of one analyte in the sample did not affect the concentration of other analytes. Total analytical time was 2.5 min, and retention times of all analytes were shorter than 2 minutes.Conclusion. This LC-MS/MS method can be preferable for therapeutic drug monitoring of these immunosuppressive drugs (CyA, TRL, SRL, and RAD) in whole blood. Sample preparation was too short and simple in this method, and it permits robust, rapid, sensitive, selective, and simultaneous determination of these drugs.

PSV-4 Determination of Deoxynivalenol (DON) Content in Biological Samples as an Indicator of DON Intake in Grower-finisher Pigs

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 206-207
Author(s):  
Michael O Wellington ◽  
Michael A Bosompem ◽  
Veronika Nagl ◽  
Daniel A Columbus
Keyword(s):  
Mass Spectrometry ◽  
Biological Samples ◽  
High Performance ◽  
Tandem Mass ◽  
Serum Samples ◽  
Blood Samples ◽  
Swine Diets ◽  
Direct Quantification ◽  
Serum And Urine

Abstract Due to difficulties in obtaining consistent and/or reliable measures of deoxynivalenol (DON) in complete swine diets, we investigated whether measuring DON in biological samples could be used as an indicator of DON ingestion in pigs. In this study, graded levels of DON (1, 3, or 5 ppm) were fed to grower-finisher pigs for a period of 77-d. On d 35 and 77 of the study, urine samples were quantitatively collected over a 24-h period and blood samples were collected between 3 – 4 h after the morning meal on each of those days for serum DON analysis. For direct quantification of DON in urine, high-performance liquid chromatography with tandem mass spectrometry was performed. For serum samples, indirect quantification of DON was performed via enzymatic hydrolysis. We observed that DON content in urine increased linearly as intake of DON increased (Fig.1A; P < 0.05). Analysis of DON in serum follow a similar trend, where serum DON content was increased as DON intake increased (Fig.1B; P < 0.05). An average of 30% of DON ingested was recovered as DON in urine over a 24-h period. In summary, there was a linear relationship between DON intake and DON content in both urine and blood serum, therefore, analyzing DON concentration in serum and urine could be used as a tool to estimate for DON exposure in pigs under controlled conditions.

scholarly journals Sex differences in serum levels of 5α-androstane-3β, 17β-diol, and androstenediol in the young adults: A liquid chromatography–tandem mass spectrometry study

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261440
Author(s):  
Haruka Tanabe ◽  
Hitoshi Mutai ◽  
Daimei Sasayama ◽  
Hidehiko Sasamoto ◽  
Yoshimichi Miyashiro ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sex Differences ◽  
Menstrual Cycle ◽  
Rating Scale ◽  
Serum Levels ◽  
Tandem Mass ◽  
Blood Samples ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Hamilton Rating Scale

Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERβ include 5α-androstane-3β, 17β-diol (3βAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3βAdiol and Δ5-diol in young healthy volunteers using liquid chromatography–tandem mass spectrometry (LC–MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC–MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17β-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3βAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3βAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3βAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3βAdiol and E2 levels, not by Δ5-diol level.

scholarly journals Differences of Phenylalanine Concentrations in Dried Blood Spots and in Plasma: Erythrocytes as a Neglected Component for This Observation

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 680
Author(s):  
Dorothea Haas ◽  
Jana Hauke ◽  
Kathrin V. Schwarz ◽  
Lucia Consalvi ◽  
Friedrich K. Trefz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Dried Blood Spots ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Tandem Mass ◽  
Blood Samples ◽  
Blood Spots ◽  
Edta Plasma

Monitoring phenylalanine (Phe) concentrations is critical for the management of phenylketonuria (PKU). This can be done in dried blood spots (DBS) or in EDTA plasma derived from capillary or venous blood. Different techniques are used to measure Phe, the most common being flow-injection analysis tandem mass spectrometry (FIA-MS-MS) and ion exchange chromatography (IEC). Significant differences have been reported between Phe concentrations in various sample types measured by different techniques, the cause of which is not yet understood. We measured Phe concentrations in 240 venous blood samples from 199 patients with hyperphenylalaninemia in dried blood spots, EDTA plasma and erythrocytes by FIA-MS-MS and IEC. Phe concentrations were significantly lower in erythrocytes than in plasma leading to about 19% lower Phe DBS concentrations compared with plasma independent from the method used for quantification. As most therapy recommendations for PKU patients are based on plasma concentrations reliable conversion of DBS into plasma concentrations is necessary. Variances of Phe concentrations in plasma and DBS are not linear but increases with higher concentrations indicating heteroscedasticity. We therefore suggest the slope of the 75th percentile from quantile regression as a correction factor.

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