Development a validated highly sensitive LC–MS/MS method for simultaneous quantification of Ledipasvir, sofosbuvir and its major metabolite GS-331007 in human plasma: Application to a human pharmacokinetic study

Abdallah, Ola M.; Abdel‐Megied, Ahmed M.; Gouda, Amira S.

doi:10.1016/j.jpba.2017.06.005

Cited by 40 publications

(25 citation statements)

References 15 publications

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“…Some analytical methods have been published for the estimation of SR and its metabolite, or in combination with other antiviral agents in biological samples [10,11,12]. One of these methods achieved a retention time of 3.5 min and achieved linear ranges of 5.0–2500 μg/L and 25–5000 μg/L for SF and GS331007, respectively.…”

Section: Introductionmentioning

confidence: 99%

Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma

et al. 2019

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A simple, fast and highly sensitive RP-UPLC-MS/MS method was developed and validated for the simultaneous determination of sofosbuvir (SR) and its metabolite GS331007 in human plasma using ketotifen as an internal standard (IS). The separation was achieved on Acquity UPLC BEH C18 (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) column using acetonitrile:5 mM ammonium formate:0.1% formic acid (85:15:0.1% v/v/v) as a mobile phase at a flow rate of 0.35 mL/min in an isocratic elution. The Xevo TQD UPLC-MS/MS was operated under the multiple-reaction monitoring mode using positive electrospray ionization. Extraction with dichloromethane was used in the sample preparation. Method validation was performed as per the Food and Drug Administration (FDA) guidelines and the calibration curves of the proposed method were found to be linear in the range of 1–1000 ng/mL for SR and in the range of 10–1500 ng/mL for its metabolite (GS331007) with an elution time of 1.83 min. All validation parameters were within the acceptable range according to the bioanalytical methods validation guidelines. Furthermore, the obtained results of matrix effects indicate that ion suppression or enhancement from human plasma components was negligible under the optimized conditions. The proposed method can be applied in high-throughput analysis required for pharmacokinetic and bioequivalence studies in human samples.

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Section: Introductionmentioning

confidence: 99%

Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma

et al. 2019

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“…5 Due to its recent introduction in the market, few techniques were reported for LDS estimation including chromatographic, 6-9 spectrophotometric 10,11 and spectrouorimetric methods. [12][13][14] Although the reported chromatographic techniques are sensitive enough, [6][7][8] they are subject to extraction procedures as the plasma samples contain a high content of phospholipids as well as it requires expensive organic solvents and long operating time. 15 In addition, all the reported UV methods were restricted to the estimation of LDS in the tablets dosage only without extension to biological uids analysis due to their limited selectivity and sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Novel spectrofluorimetric approach for determination of ledipasvir through UV-irradiation: application to biological fluids, pharmacokinetic study and content uniformity test

et al. 2019

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“…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…”

Section: Introductionmentioning

confidence: 99%

Development and validation of LC‐MS/MS method for simultaneous determination of sofosbuvir and daclatasvir in human Plasma: Application to pharmacokinetic study

Abdallah

Abdel‐Megied

Gouda³

2018

Biomedical Chromatography

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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.

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Development a validated highly sensitive LC–MS/MS method for simultaneous quantification of Ledipasvir, sofosbuvir and its major metabolite GS-331007 in human plasma: Application to a human pharmacokinetic study

Cited by 40 publications

References 15 publications

Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma

Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma

Novel spectrofluorimetric approach for determination of ledipasvir through UV-irradiation: application to biological fluids, pharmacokinetic study and content uniformity test

Development and validation of LC‐MS/MS method for simultaneous determination of sofosbuvir and daclatasvir in human Plasma: Application to pharmacokinetic study

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