Dataset Information

Novel LC-MS/MS method for analysis of metformin and canagliflozin in human plasma: application to a pharmacokinetic study.

ABSTRACT: Highly sensitive and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous estimation of the recently approved oral hypoglycemic mixture; metformin (MET) and canagliflozin (CFZ) in human plasma using propranolol HCl (PPL) and tadalafil (TDF) as internal standards (IS), respectively. Analytes were extracted using protein precipitation induced by acetonitrile then liquid-liquid extraction was performed using ethyl acetate. Reversed phase HPLC was carried out using C18 analytical column (50 mm?×?4.6 mm i.d., 5 µm) with a simple isocratic mobile phase composed of 0.1% formic acid and acetonitrile (60:40, v/v). Detection was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in multiple reaction monitoring (MRM), with the transitions of m/z 130.2???60.1, m/z 462.3???191.0, m/z 260.2???183.0 and m/z 390.2???268.2 for MET, CFZ, PPL and TDF, respectively, in the positive ion mode. The analysis was carried out within 5 min over a linear concentration range of 50-5000 ng/mL for MET and 10-1000 ng/mL for CFZ. The method was validated in accordance with the FDA guidelines for bioanalytical method. All obtained recoveries were higher than 90.0% while the accuracy was in the range of 88.14-113.05% and the relative standard deviation was below 10.0% for all investigated drugs by the proposed method. The achieved promising results has allowed for the successful application of the developed LC-MS/MS method to a pharmacokinetic study of the target drugs after their oral administration to Egyptian healthy volunteers. The pharmacokinetic study was accomplished after the agreement of the ethics committee.

SUBMITTER: Mohamed D

PROVIDER: S-EPMC6661773 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Novel LC-MS/MS method for analysis of metformin and canagliflozin in human plasma: application to a pharmacokinetic study.

Mohamed Dalia D Elshahed Mona S MS Nasr Tamer T Aboutaleb Nageh N Zakaria Ola O

BMC chemistry 20190709 1

Highly sensitive and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous estimation of the recently approved oral hypoglycemic mixture; metformin (MET) and canagliflozin (CFZ) in human plasma using propranolol HCl (PPL) and tadalafil (TDF) as internal standards (IS), respectively. Analytes were extracted using protein precipitation induced by acetonitrile then liquid-liquid extraction was performed using ethyl acetate. Rever ...[more]

PMID: 31384829

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Project description:A fully validated, simple, rapid and reproducible liquid chromatography-tandem mass spectrometry method was developed to determine NHC (N-hydroxycytidine), the active metabolite of Molnupiravir (MOL) in human plasma; one of the limited treatment options for SARS-CoV-2 in plasma of healthy volunteers. The internal standard (IS) used was ribavirin. The extraction of analyte and IS from plasma was performed using acetonitrile as a solvent for protein precipitation. Agilent Zorbax Eclipse plus C18, 4.6 × 150 mm, (5 µm) was used for chromatographic separation using a mixture of methanol0.2 % acetic acid (5:95, v/v) as a mobile phase that was pumped at a flow rate of 0.9 mL/min. Detection was performed on a triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) employing positive ESI interface using API4500 triple quadrupole tandem mass spectrometer system, with the transitions set at m/z 260.10 → 128.10 and 245.10 → 113.20 for NHC and IS respectively. Method validation was performed in accordance with United States FDA bioanalytical guidance. The concentration range of 20.0-10000.0 ng/mL was used to establish linearity via weighted linear regression approach (1/x2). Moreover, the analyzed pharmacokinetic data from twelve Egyptian healthy volunteers were used to develop a population pharmacokinetic model for NHC. The developed model was used to perform simulations and evaluate the current MOL dosing recommendations through calculating the maximum concentration (Cmax) "the safety metric" and area under the curve (AUC0-12 h) "the efficacy metric" for 1000 virtual subjects. Geometric mean ratios (GMR) with their associated 90% confidence intervals (CI) compared to literature values were computed. Geometric means of simulation-based Cmax and AUC0-12 were 3827 ng/mL (GMR = 1.05; 90% CI = 0.96-1.15) and 9320 ng.h/mL (GMR = 1.04; 90% CI = 0.97-1.11), respectively indicating that current MOL dosage can achieve the therapeutic targets and dose adjustment may not be required for the Egyptian population. The developed model could be used in the future to refine MOL dosage once further therapeutic targets are identified.

Dataset Information

Novel LC-MS/MS method for analysis of metformin and canagliflozin in human plasma: application to a pharmacokinetic study.

Publications

Novel LC-MS/MS method for analysis of metformin and canagliflozin in human plasma: application to a pharmacokinetic study.

Similar Datasets

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