Search

Showing total 876 results
Start Over Topic pharmacokinetics Publisher springer berlin heidelberg
876 results

2. Quantitative HPLC-MS/MS determination of Nuc, the active metabolite of remdesivir, and its pharmacokinetics in rat

Author

Song Yang, Pengfei Li, Ping Du, Lihong Liu, and Guoyong Wang

Subjects
Male, Quality Control, Electrospray, Adenosine, Remdesivir, Biochemistry, Antiviral Agents, Analytical Chemistry, Quantitation, Rats, Sprague-Dawley, Pharmacokinetics, Limit of Detection, Tandem Mass Spectrometry, Nuc, Protein precipitation, Animals, Active metabolite, Chromatography, High Pressure Liquid, Reproducibility, Chromatography, Alanine, Chemistry, HPLC-MS/MS, Selected reaction monitoring, Reproducibility of Results, Prodrug, Reference Standards, Adenosine Monophosphate, Rats, Quantitative analysis (chemistry), Research Paper
Abstract

Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 μm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg−1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstract

Published
2021

4. Signal Enhancement in the HPLC-ESI-MS/MS analysis of spironolactone and its metabolites using HFIP and NH4F as eluent additives

Author

Jana Lass, Heili Varendi, Lenne-Triin Kõrgvee, Rudolf Aro, Karin Kipper, Kalev Takkis, and Koit Herodes

Subjects
Analyte, Spectrometry, Mass, Electrospray Ionization, Ammonium fluoride, Signal enhancement, 030204 cardiovascular system & hematology, Spironolactone, 01 natural sciences, Biochemistry, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Column chromatography, Pharmacokinetics, Limit of Detection, Tandem Mass Spectrometry, Canrenone, Blood plasma, medicine, Protein precipitation, Humans, Sample preparation, Liquid chromatography-mass spectrometry, Chromatography, High Pressure Liquid, Mineralocorticoid Receptor Antagonists, Chromatography, Chemistry, 010401 analytical chemistry, 3. Good health, 0104 chemical sciences, Hexafluoroisopropanol, Ionization efficiency, medicine.drug, Research Paper
Abstract

This paper describes an LC-MS/MS method to determine the concentration of spironolactone and its metabolites 7-alpha-methylthiospironolactone and canrenone in blood plasma samples. The resulting assay is simple (using protein precipitation for sample preparation) and sensitive (the lower limit of quantification is close to 0.5 ng/ml) while requiring only 50 μl of plasma, making it especially suitable for analyzing samples obtained from pediatric and neonatal patients where sample sizes are limited. The sensitivity is achieved by using ammonium fluoride as an eluent additive, which in our case amplifies the signal from our analytes in the plasma solution on average about 70 times. The method is fully validated according to the European Medicines Agency’s guideline and used for the measurement of pediatric patients’ samples in clinical trials for evaluating oral spironolactone’s and its metabolites’ pharmacokinetics in children up to 2 years of age.

Published
2017

8. Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data

Author

Felix Lötsch, Klaus Kaczirek, Fredrik Waneck, Herbert Auer, Judith Naderer, Mirjam Groger, Tomislava Skuhala, and Michael Ramharter

Subjects
0301 basic medicine, Drug, medicine.medical_specialty, Pathology, Drug concentration, media_common.quotation_subject, 030231 tropical medicine, Albendazole-sulphoxide, Albendazole, Gastroenterology, Praziquantel, Cystic echinococcosis, Echinococcus granulosus, Hydatid disease, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Echinococcosis, Internal medicine, medicine, Animals, Humans, Cyst, media_common, Anthelmintics, Original Paper, General Veterinary, biology, business.industry, Cysts, General Medicine, 030108 mycology & parasitology, medicine.disease, biology.organism_classification, Infectious Diseases, Insect Science, Parasitology, Hepatic Cyst, business, medicine.drug
Abstract

Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)—the first-line anthelminthic drug for medical treatment of CE—is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = −0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 μg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 μg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 μg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (β = −17.2 μg/L/cm; 95th CI, −35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis. Electronic supplementary material The online version of this article (doi:10.1007/s00436-016-5054-x) contains supplementary material, which is available to authorized users.

Published
2016