Abstract:A quantitative strategy towards the detection of sofosbuvir in human plasma was developed with online-SPE-LC-HRMS using t-MS2, t-SIM and F-SIM modes.
“…These data could be useful for further MS-based analysis in order to enhance selectivity and sensitivity when more complex biological samples are analyzed. In this sense, sofosbuvir is typically analyzed in plasma using ESI in the positive ion mode [8] , [9] , [10] although the negative ionization mode also seems a potential alternative. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Liquid chromatography (LC) coupled to UV detection or mass spectrometry (MS) has been applied to determine oral anti-HCV drugs in pharmaceutical preparations [6] , biological samples [7] , [8] , [9] , [10] or even in wastewater [11] . In these studies, reversed phase (RP) liquid chromatography using silica-based C 18 columns is the most common mode.…”
Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus (HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be produced by local drug producers in some countries. Therefore, new methods are required to control sofosbuvir in pharmaceuticals. In the present study, a new method based on reversed phase (RP)-ultra-high performance liquid chromatography (UHPLC) coupled to diode array detection (DAD) and mass spectrometry (MS) was developed to facilitate the qualitative and quantitative analysis of sofosbuvir in film coated tablets. A wavelength of 260 nm was selected to perform a cost-effective quantification and the method showed adequate linearity, with an R2 value of 0.9998, and acceptable values of accuracy (75%–102%) and precision (residual standard deviation <5%). The detection and quantification limits were 0.07 μg/mL and 0.36 μg/mL, respectively. Furthermore, the use of high-resolution MS enabled us to ensure the specificity, check impurities and better sensitivity. Therefore, this methodology promises to be suitable not only for the routine analysis of sofosbuvir in pharmaceutical dosage forms, but also for potential degradants.
“…These data could be useful for further MS-based analysis in order to enhance selectivity and sensitivity when more complex biological samples are analyzed. In this sense, sofosbuvir is typically analyzed in plasma using ESI in the positive ion mode [8] , [9] , [10] although the negative ionization mode also seems a potential alternative. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Liquid chromatography (LC) coupled to UV detection or mass spectrometry (MS) has been applied to determine oral anti-HCV drugs in pharmaceutical preparations [6] , biological samples [7] , [8] , [9] , [10] or even in wastewater [11] . In these studies, reversed phase (RP) liquid chromatography using silica-based C 18 columns is the most common mode.…”
Sofosbuvir is one of the new direct-acting antiviral drugs against hepatitis C virus (HCV) infection. This drug has recently been launched into the market, and generic versions of the medication are expected to be produced by local drug producers in some countries. Therefore, new methods are required to control sofosbuvir in pharmaceuticals. In the present study, a new method based on reversed phase (RP)-ultra-high performance liquid chromatography (UHPLC) coupled to diode array detection (DAD) and mass spectrometry (MS) was developed to facilitate the qualitative and quantitative analysis of sofosbuvir in film coated tablets. A wavelength of 260 nm was selected to perform a cost-effective quantification and the method showed adequate linearity, with an R2 value of 0.9998, and acceptable values of accuracy (75%–102%) and precision (residual standard deviation <5%). The detection and quantification limits were 0.07 μg/mL and 0.36 μg/mL, respectively. Furthermore, the use of high-resolution MS enabled us to ensure the specificity, check impurities and better sensitivity. Therefore, this methodology promises to be suitable not only for the routine analysis of sofosbuvir in pharmaceutical dosage forms, but also for potential degradants.
“…Exposure of the SOF metabolite (GS‐331007) was similar in the presence and absence of DAC, while SOF exposures were ~35% higher in the presence of DAC (http://www.hcvdruginfo.ca/downloads/Hepatitis%20Cint_new%20NS5A%20inhibitors.pdf). The published methods for determination of SOF and/or DAC in human plasma are HPLC (Baker, El‐Kafrawy, Mahrous, & Belal, ; Hassib, Taha, Elkady, & Barakat, ; Nannetti et al, ; Srinivasu, Kumar, & Thirupathi, ), LC‐MS/MS (Abdallah, Abdel‐Megied, & Gouda, ; Ariaudo et al, ; Jiang et al, ; Nebsen & Elzanfaly, ; Qu, Wang, Zeng, Lub, & Yin, ; Rezk et al, , , b; Shi et al, ) and electrochemical detection (Azab & Fekry, ). To author's knowledge, this bio‐analytical method is the only LC‐MS/MS method for determination of SOF and DAC in human plasma with application to a pharmacokinetic study for both.…”
Section: Introductionmentioning
confidence: 99%
“…However, NS5A has no known enzymatic functions and so it is difficult to understand its mode of action (Belema et al, 2014;Smith, Regal, & Mohammad, 2016; Figure 1). There are eight metabolites of DAC, one of which (BMS-805215) has some activity; however, it is 100-fold less potent than the parent drug (Product monograph, 2016 (Baker, El-Kafrawy, Mahrous, & Belal, 2017;Hassib, Taha, Elkady, & Barakat, 2017;Nannetti et al, 2017;Srinivasu, Kumar, & Thirupathi, 2016), LC-MS/MS (Abdallah, Abdel-Megied, & Gouda, 2017;Ariaudo et al, 2016;Jiang et al, 2015;Nebsen & Elzanfaly, 2016;Qu, Wang, Zeng, Lub, & Yin, 2015;Rezk et al, 2015Shi et al, 2015) and electrochemical detection (Azab & Fekry, 2017…”
A simple and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method was developed and fully validated for the first time for the simultaneous determination of newly discovered antiviral drugs, namely sofosbuvir (SOF) and daclatasvir (DAC) in human plasma. Tadalafil (TAD) was used as internal standard (IS). SOF, DAC and TAD (IS) were extracted from plasma using liquid-liquid extraction technique with methyl tert-butyl ether. The chromatographic separation was carried out using ZorbaxSB-C column (4.6 × 50 mm,5 μm) and 5 mm ammonium formate buffer (pH 3.5)-acetonitrile (50:50, v/v) as mobile phase in an isocratic elution mode pumped at a flow rate 0.7 mL min . The quantitation was performed on API4500 triple quadrupole tandem mass spectrometer with positive electrospray ionization interface in multiple reaction monitoring mode. Validation was applied according to US Food and Drug Administration guidelines for bio-analytical methodswith respect to linearity, precision, accuracy, selectivity, carry-over, stability and dilution integrity. Linearity was obtained over concentration ranges of 0.3-3000 and 3-3000 ng mL for SOF and DAC, respectively, by applying a weighted least-squares linear regression method (1/x ). The proposed method could be applied successfully in bioequivalence and/or clinical studies for therapeutic drug monitoring of patients undergoing dual combination therapy as the latter combination proved more efficacious and powerful tool for the complete treatment of hepatitis C genotype 3 within 16 weeks. The suggested method has been applied successfully to pharmacokinetic studies with excellent assay ruggedness and reproducibility.
“…A literature review revealed a few methods have been reported for the quantitative determination of DAC and LED alone or in combination with other drugs. These include spectrophotometric, spectrofluorimetric, HPLC,, LC–MS/MS and electrochemical methods . The extensive use of the newly discovered antiviral drugs for the treatment of HCV necessitates the need to develop a cheap, rapid bio‐analytical method for their routine measurement in biological samples.…”
A simple, highly sensitive and selective spectrofluorimetric method has been developed and fully validated for the determination of daclatasvir (DAC) and ledipasvir (LED) in tablets and human plasma. The method is based on measurement of the native fluorescence in methanol at λ 384 nm after excitation at λ 318 nm for DAC and in acetonitrile at λ 402 nm after excitation at λ 340 nm for LED. The fluorescence intensity (FI) concentration plot was rectilinear over the ranges 1.2-12, 0.1-18 ng ml and 9-90, 1-100 ng ml with a good correlation of r = 0.9994 to r = 0.9997 in standard solution and human plasma for DAC and LED, respectively. The extraction of analytes from plasma was performed using methanol and acetonitrile as a precipitating agent with lower limit of quantification (LLOQ) of 0.1 and 1.0 ng ml for DAC and LED; respectively. The proposed method was validated according to the US Food and Drug Administration (FDA) guidelines and successfully applied for estimating the pharmacokinetic parameters of DAC and LED following oral administrations of their tablets.
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