UPLC–MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients

Notari, Stefania; Tempestilli, Massimo; Fabbri, Gioele; Libertone, Raffaella; Antinori, Andrea; Ammassari, Adriana; Agrati, Chiara

doi:10.1016/j.jchromb.2017.12.018

Cited by 35 publications

(18 citation statements)

References 27 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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“…HCV infection causes the activation of immune cells, and leads to the increased secretion of hs-CRP through positive feedback. In HCV infection, especially in the acute infection period (17), the acute inflammatory response induced by hs-CRP will further aggravate hepatocellular injury and cause cirrhosis, even hepatoma (18). HIV infection will mainly inhibit the function of CD4 + T lymphocytes, and lead to immune tolerance and the lack of effective defensive ability of the body, then lead to a decrease in the ability of the body to recognize and eliminate HCV and an increase of the replication of HCV, and this will further cause an increase in hs-CRP level, while a decrease in CD4 + level (19).…”

Section: Discussionmentioning

confidence: 99%

Changes of body immunity and inflammatory response in HIV/HCV co-infected patients

2018

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Changes of body immunity and inflammatory response in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients were investigated. Eighty HIV/HCV infected patients admitted to Qingdao No. 6 People's Hospital from August 2015 to December 2017 were selected and divided into two groups according to whether they were complicated with HCV infection or not (n=40 per group). The changes of the related humoral immune indexes, the related cellular immune indexes, the related indexes of hepatic function, the related indexes of inflammatory response in the two groups were compared, and the correlations of high-sensitivity C-reactive protein (hs-CRP) level with alanine aminotransferase (ALT) level, immunoglobulin G (IgG) level and cluster of differentiation 4+ (CD4+) level in the observation group were analyzed. The levels of related humoral immune indexes [immunoglobulin G (IgG), IgA and IgM levels], the related cellular immune indexes (CD4+ and CD8+) in the observation group were lower than those in the control group (P<0.05), and the CD4+/CD8+ ratio in the observation group was lower than that in the control group (P<0.05). The levels of indexes of hepatic function [ALT, aspartate aminotransferase (AST) and total bilirubin] in the observation group were significantly higher than those in the control group (P<0.05). The levels of hs-CRP, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) in the observation group were significantly higher than those in the control group (P<0.05). There were positive correlations of hs-CRP level with ALT level and IgG level in the observation group (P<0.05). There was a negative correlation between hs-CRP level and CD4+ level in the observation group (P<0.05). The humoral and cellular immune functions of the HIV/HCV co-infected patients are significantly limited, their hepatic function is significantly impaired and the levels of inflammatory cytokines are markedly increased. The level of hs-CRP is positively correlated with hepatic function and humoral immune function and negatively correlated with cellular immune function.

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“…Ctrough were determined for SOF, GS-331007, and DCV using a validated UPLC-MS/MS method. Limit of quantification were 11.71 ng/mL for SOF and DCV, and 19.53 ng/mL for GS-331007 [14].…”

Section: Daa Plasma Concentrationsmentioning

confidence: 96%

Drug plasma trough concentrations during treatment with daclatasvir and sofosbuvir are associated respectively with liver impairment and with renal dysfunction in HIV/HCV co-infected patients

Mastrorosa¹,

Tempestilli²,

Notari³

et al. 2019

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Background Sofosbuvir (SOF) plus daclatasvir (DCV) achieved high rates of sustained virologic response (SVR) with no difference according to HIV serostatus. Only limited information is available on the pharmacokinetics variability of SOF and DCV in HIV/HCV co-infected patients. Aim was to evaluate the association of plasma drug concentrations (Ctrough) of SOF and of DCV with patient-, treatment-, and disease-related factors in the real-world setting of HIV/HCV co-infected persons. Methods HIV/HCV co-infected patients, undergoing SOF plus DCV treatment, were prospectively enrolled. At baseline, week4 (W4), end of treatment (EOT), and after-EOT, biochemical and viro-immunological parameters were assessed. FIB-4 score and CKD-EPI equation were used for estimation of liver disease and glomerular filtration rate (eGFR), respectively. SOF, SOF metabolite (GS-331007), and DCV Ctrough were measured at W4 and week8 (W8), and the mean value (mean-Ctrough) was calculated Results Thirty-five patients were included (SVR 94%). Increasing GS-331007 mean-Ctrough significantly correlated with decreasing eGFR at W4 (rho=-0.36; p=0.037) and EOT (rho=-0.34; p=0.048). Between DCV mean-Ctrough and FIB-4, a significant correlation was observed at all time-points: baseline (rho=-0.35; p=0.037), W4 (rho=-0.44; p=0.008), EOT (rho=-0.40; p=0.023), after-EOT (rho=-0.39; p=0.028). Conclusion In HIV/HCV co-infected patients receiving SOF plus DCV, plasma drug concentrations are associated with renal dysfunction for GS-331007 and with liver impairment for DCV. Though clinical and therapeutically relevance of these findings may apparently be limited, growth of clinicians’ knowledge on DAA exposure in difficult-to-treat patients, as cirrhotic and renal impaired subjects, can be relevant in single cases.

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UPLC–MS/MS method for the simultaneous quantification of sofosbuvir, sofosbuvir metabolite (GS-331007) and daclatasvir in plasma of HIV/HCV co-infected patients

Cited by 35 publications

References 27 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

Changes of body immunity and inflammatory response in HIV/HCV co-infected patients

Drug plasma trough concentrations during treatment with daclatasvir and sofosbuvir are associated respectively with liver impairment and with renal dysfunction in HIV/HCV co-infected patients

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