Simultaneous quantification of Darunavir and Ritonavir in human plasma and pharmacokinetic study by LC MS/MS
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Title |
Simultaneous quantification of Darunavir and Ritonavir in human plasma and pharmacokinetic study by LC MS/MS
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Creator |
Amarnath
Srivastava, Anupam Kumar Ameta, Suresh C Ameta, Rakshit |
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Subject |
Bioanalytical
Bioequivalence Darunavir (DRV) Good Clinical Practice LCMS/MS method Validation Lower Limit of Quantification Pharmacokinetic, Ritonavir (RTV) |
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Description |
285-296
The combination of Darunavir (DRV) and Ritonavir (RTV) at a dose of 800/100mg has exhibit durable efficacy in both untreated and treated HIV positive patients with no observed DRV resistance-associated mutations (RAMs) and the RTV improves the pharmacokinetic profile of DRV by enhancing its bioavailability. Hence a sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the simultaneous quantification of Darunavir (DRV) and Ritonavir (RTV) in human plasma. The chromatographic separation has been accomplished on Thermo Hypersil Gold (50×4.6mm, 3μ) analytical column using isocratic elution using 0.1% Formic Acid buffer solution/Acetonitrile (50:50, v/v) at a flow rate of 0.6 mL/min. The linearity of the method ranged 150.000 ng/mL to 15000.000 ng/mL & 10.000 ng/mL to 3000.00 ng/mL for DRV & RTV respectively, using 100 μL of plasma. The method was completely validated for its sensitivity, selectivity, linearity, accuracy and precision, recovery, matrix effect, stability, and dilution integrity. The absolute recovery for DRV ranged from 79.12 to 72.71 % while for RTV it ranged from 63.39% to 66.99 %. For DRV-D9 and RTV-D6 the recovery rates are 94.19 and 80.05% respectively. The method exhibit good intra-day and inter-day precision with low % CV of less than 5.0% at each quality control level for both the analytes. The developed method has been applied successfully for pharmacokinetic study in healthy humans by oral administration of Darunavir/Ritonavir tablets 400/50 mg (dose; 02x400/50 mg) in 77 healthy male volunteers under fed condition. |
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Date |
2021-08-05T06:35:27Z
2021-08-05T06:35:30Z 2021-08-05T06:35:27Z 2021-08-05T06:35:30Z 2021-05 |
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Identifier |
0975-0991 (Online); 0971-457X (Print)
http://nopr.niscair.res.in/handle/123456789/57843 |
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Publisher |
NIScPR-CSIR, India
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Source |
IJCT Vol.28(3) [May 2021]
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