Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Rapid Commun Mass Spectrom ; 36(12): e9282, 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1802571

ABSTRACT

RATIONALE: A derivatization switchable solvent liquid-liquid microextraction quadruple isotope dilution gas chromatography mass spectrometry (D-SS-LLME-ID4 -GC/MS) method is presented for the determination of hydroxychloroquine sulfate in human biofluids. METHODS: While mixing type/period and concentration of NaOH were optimized via a univariate optimization approach, a multivariate optimization approach was used to determine optimum values for relatively more important parameters such as volumes of derivatization agent (acetic anhydride), NaOH and switchable solvent. RESULTS: Under the optimum experimental conditions, limit of detection and limit of quantification were calculated as 0.03 and 0.09 mg/kg (mass based), respectively. An isotopically labelled material (hydroxychloroquine methyl acetate-d3 ) was firstly synthesized to be used in ID4 experiments which give highly accurate and precise recovery results. After the application of D-SS-LLME-ID4 , superior percent recovery results were recorded as 99.9 ± 1.6-101.3 ± 1.2 for human serum, 99.9 ± 1.7-99.8 ± 1.8 for urine and 99.6 ± 1.5-101.0 ± 1.1 for saliva samples. CONCLUSIONS: The developed D-SS-LLME-ID4 -GC/MS method compensates the complicated matrix effects of human biofluids and provides highly accurate quantification of an analyte with precise results.


Subject(s)
Liquid Phase Microextraction , Acetates , Gas Chromatography-Mass Spectrometry/methods , Humans , Hydroxychloroquine , Isotopes , Limit of Detection , Liquid Phase Microextraction/methods , Sodium Hydroxide , Solvents/chemistry
2.
Biomed Chromatogr ; 36(6): e5365, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1739127

ABSTRACT

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid-liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 µl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 105  ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.


Subject(s)
COVID-19 , Ionic Liquids , Liquid Phase Microextraction , Amides , COVID-19/drug therapy , Chromatography, High Pressure Liquid/methods , Furans , Gadolinium , Humans , Liquid Phase Microextraction/methods , Magnetic Phenomena , Pyrazines
3.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1189: 123087, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1587335

ABSTRACT

Favipiravir is a promising antiviral agent that has been recently approved for treatment of COVID-19 infection. In this study, a menthol-assisted homogenous liquid-liquid microextraction method has been developed for favipiravir determination in human plasma using HPLC/UV. The different factors that could affect the extraction efficiency were studied, including extractant type, extractant volume, menthol amount and vortex time. The optimum extraction efficiency was achieved using 300 µL of tetrahydrofuran, 30 mg of menthol and vortexing for 1 min before centrifuging the sample for 5 min at 3467g. Addition of menthol does not only induce phase separation, but also helps to form reverse micelles to facilitate extraction. The highly polar favipiravir molecules would be incorporated into the hydrophilic core of the formed reverse micelle to be extracted by the non-polar organic extractant. The method was validated according to the FDA bioanalytical method guidelines. The developed method was found linear in the concentration range of 0.1 to 100 µg/mL with a coefficient of determination of 0.9992. The method accuracy and precision were studied by calculating the recovery (%) and the relative standard deviation (%), respectively. The recovery (%) was in the range of 97.1-103.9%, while the RSD (%) values ranged between 2.03 and 8.15 %. The developed method was successfully applied in a bioequivalence study of Flupirava® 200 mg versus Avigan® 200 mg, after a single oral dose of favipiravir administered to healthy adult volunteers. The proposed method was simple, cheap, more eco-friendly and sufficiently sensitive for biomedical application.


Subject(s)
Amides/isolation & purification , Antiviral Agents/isolation & purification , COVID-19/drug therapy , Liquid Phase Microextraction/methods , Pyrazines/isolation & purification , Amides/administration & dosage , Amides/blood , Antiviral Agents/administration & dosage , Antiviral Agents/blood , COVID-19/blood , COVID-19/virology , Chromatography, High Pressure Liquid/methods , Humans , Liquid Phase Microextraction/instrumentation , Menthol/chemistry , Pyrazines/administration & dosage , Pyrazines/blood , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
4.
J Sep Sci ; 44(9): 1961-1968, 2021 May.
Article in English | MEDLINE | ID: covidwho-1527448

ABSTRACT

In this study, a lab-made parallel single-drop microextraction methodology using the magnetic ionic liquid trihexyltetradecylphosphonium tetrachloromanganate (II) as extraction solvent was developed to determine the pesticides tebuconazole, pendimethalin, dichlorodiphenyltrichloroethane, and dichlorodiphenyldichloroethylene in human urine samples. The experimental setup consisted of a 96-well plate system containing a set of magnetic pins that allowed for the manipulation of up to 96 samples simultaneously, providing an enhanced drop stability compared to traditional single-drop microextraction approaches. The optimal conditions employed 5.38 ± 0.55 mg of extraction solvent, 1.5 mL of diluted urine samples (1:10), extraction time of 130 min, and subsequent dilution in 20 µL of acetonitrile. The method exhibited satisfactory analytical performance, with limits of detection of 7.5 µg/L for all analytes and coefficients of determination higher than 0.9955. Intraday and interday precisions ranged from 3 to 17% (n = 3) and 15 to 18% (n = 9), respectively, with relative recovery of analytes ranging from 70 to 122%. The method proposed was successfully applied in two human urine samples and no sign of the analytes was detected. The results demonstrated that the proposed method allowed for cost-effective and high-throughput methodology to be explored as a valuable tool in bioanalytical applications.


Subject(s)
Biological Monitoring/methods , Liquid Phase Microextraction/methods , Pesticides , COVID-19 , Humans , Limit of Detection , Pesticides/analysis , Pesticides/urine
5.
J Pharmacol Toxicol Methods ; 113: 107130, 2022.
Article in English | MEDLINE | ID: covidwho-1475116

ABSTRACT

In the present study, a novel analytical method for the determination of hydroxychloroquine sulfate in human serum and urine samples was established. One step derivatization and dispersive liquid-liquid microextraction (DLLME) was developed for quantitative determination of hydroxychloroquine sulfate in aqueous samples. Hydroxychloroquine sulfate was first hydrolyzed and converted to its benzoate derivative by adding benzoyl chloride in chloroform which also served as extraction solvent. Significant parameters such as type/volume of extraction and dispersive solvents, concentration/volume of sodium hydroxide, type/period of mixing and concentration of derivatizing agent were carefully optimized by one variable at a time approach. Under the optimum DLLME conditions, limit of detection (LOD), quantitation (LOQ) and dynamic range were calculated as 35.2, 117.2 and 96-1980 µg/kg (ppb), respectively. Recovery studies were conducted by spiked human serum and urine samples and the results were ranged between 93 and 107% with low standard deviations. Developed method can be easily used in hydroxychloroquine sulfate based SARS-CoV-2 and malaria treatment studies.


Subject(s)
COVID-19 , Liquid Phase Microextraction , COVID-19/drug therapy , Gas Chromatography-Mass Spectrometry , Humans , Hydroxychloroquine , Limit of Detection , SARS-CoV-2 , Solvents
6.
J Pharmacol Toxicol Methods ; 108: 106949, 2021.
Article in English | MEDLINE | ID: covidwho-1045104

ABSTRACT

A vortex assisted spraying based fine droplet formation liquid phase microextraction (VA-SFDF-LPME) method was developed to determine chloroquine phosphate at trace levels in human serum, urine and saliva samples by gas chromatography-mass spectrometry (GC-MS) with single quadrupole mass analyzer. In the first part, several liquid phase microextraction (LPME) and magnetic solid phase extraction (MSPE) methods were compared to each other in order to observe their extraction ability for the analyte. VA-SFDF-LPME method was selected as an efficient and easy extraction method due to its higher extraction efficiency. Optimization studies were carried out for the parameters such as extraction solvent type, sodium hydroxide volume/concentration, sample volume, spraying number and mixing type/period. Tukey's method based on post hoc test was applied to all experimental data for the selection of optimum values. Optimum extraction parameters were found to be 12 mL initial sample volume, two sprays of dichloromethane, 0.75 mL of 60 g/kg sodium hydroxide and 15 s vortex. Under the optimum conditions, limit of detection and quantification (LOD and LOQ) were calculated as 2.8 and 9.2 µg/kg, respectively. Detection power of the GC-MS system was increased by approximately 317 folds with the developed extraction/preconcentration method. The applicability and accuracy of the proposed method was evaluated by spiking experiments and percent recovery results for human urine, serum and saliva samples were found in the range of 90.9% and 114.0% with low standard deviation values (1.9-9.4).


Subject(s)
Chloroquine , Liquid Phase Microextraction , Chloroquine/analogs & derivatives , Gas Chromatography-Mass Spectrometry , Humans , Limit of Detection , Saliva
SELECTION OF CITATIONS
SEARCH DETAIL