Development And Validation Of Sensitive LC-MS/MS Method For Determination Of Doravirine In Human Plasma Samples (original) (raw)
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Analytical Method Development and Validation for Determination of Doravirine by RP-HPLC
Ymer, 2022
An easy, specific and precise RP-HPLC technique has been created and tested for the quantification of doravirine in pure and its tablet dosage forms. Doravirine is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI). It is utilized in the treatment of HIV-1 infection in combination with other antiviral medications therapies (ARTs). The separation was completed on the Agilent C18 column (150 x 4.6 mm) with 5µ particle size. 0.01N potassium dihydrogen phosphate and acetonitrile (ACN) (60:40 v/v), at a flow rate of 1ml/min, was used as an optimum mobile phase. The wavelength chosen was 210 nm. The retention time for doravirine was 2.379 min. Linearity of doravirine was found to be 25-150μg/ml. Linearity equation attained was y= 11776x+ 2813 with correlation coefficient 0.999. The relative standard deviation for precision was found to be less than 2%. % Recovery was found as 100.13% for doravirine. The LOD and LOQ for doravirine were found as 0.06 µg/ml and 0.18 µg/ml.
Determination of doravirine in human plasma using liquid–liquid extraction and HPLC–MS/MS
Bioanalysis, 2019
Aim: A method to quantitate doravirine (MK-1439) in human plasma has been developed to support human clinical trials designed to evaluate the safety, pharmacokinetics and efficacy of the compound. Methodology & results: The analyte was extracted using liquid–liquid extraction, separated on a reverse phase HPLC column, and detected on an API-4000 mass spectrometer using a Turbo-Ion spray source in positive ionization mode coupled with multiple reaction monitoring mode was used for quantification. The dynamic range for the assay was 0.02–10 ng/ml using 100 μl of human plasma. Conclusion: The assay was found to be sensitive, selective and reproducible and applied to support the doravirine clinical development program.
International Journal of Applied Pharmaceutics
Objective: In this study, a RP-HPLC (stability-indicating) based assay method for the estimation of doravirine (DRV), tenofovir disoproxil fumarate (TFF) and lamivudine (LMV) simultaneously in the tablets was described. Methods: The simultaneous analysis of DRV, TFF and LMV was done with HPLC system (Agilent 1100 series) and Luna Phenomenex C18 (250 mm × 4.6 mm × 5 μ) column with isocratic mobile phase (35% volume ratio of methanol and 65% volume ratio of 20 mmol ammonium formate, pH 5). Validation of assay method was done on sensitivity, linearity, accuracy, selectivity, precision, robustness and specificity. Results: The calibration curves were linear through the range of 25-200 µg/ml for DRV and 75-600 µg/ml for TFF and LMV. The percent relative standard deviation for intraday variation/precision, interday variation/precision, intermediate precision/ruggedness and robustness were lower than 2%. The recovery of LMV (99.09-99.76%), TFF (99.10-99.41%) and DRV (98.65-99.28%) confirme...
An HPLC method for the determination of diastereomeric prodrug RS-79070-004 in human plasma
Journal of Pharmaceutical and Biomedical Analysis, 1999
Ganciclovir is an antiviral nucleoside analogue approved for treatment and prevention of cytomegalovirus infections in immunocompromised subjects. RS-79070-194, a diastereomeric monovalyl ester of ganciclovir (hydrochloride salt), is under evaluation as a prodrug to increase the bioavailability of ganciclovir. An HPLC method with column switching has been developed and validated for quantification of the corresponding free base RS-79070-004 in human plasma. In the method, proteinaceous material in 0.25 ml of plasma is precipitated by trichloroacetic acid. An aliquot of the supernatant is analyzed by HPLC, with automated column switching to remove late-eluting materials that might interfere with the analyte peaks in subsequent runs. Detection of RS-79070-004 is by UV (u=254 nm). The peak areas for each isomer are summed to generate a value for total RS-79070-004. The method has a validated range of 0.0400-4.00 mg/ml and a lower limit of quantification of 0.0400 mg/ml. All intra-and inter-assay %CVs were B7.5%, and all recoveries (accuracy) were within 6% of nominal values. No interference was observed by ganciclovir, caffeine, acetaminophen, or ibuprofen. Analyte stability in plasma and in the sample extracts is adequate for the specified collection, storage, and analysis conditions. The validated method has been successfully used to analyze clinical study samples.
Bioanalysis, 2013
Dapivirine is a non-nucleoside reverse transcriptase inhibitor designed to prevent HIV-1 viral replication and subsequent propagation. A sensitive method is required to quantify plasma concentrations to assess drug efficacy. Dapivirine-spiked plasma was combined with acetonitrile containing deuterated IS and was processed for analysis. The method has an analytical measuring range from 20 to 10,000 pg/ml. For the LLOQ, low, mid and high QCs, intra- and inter-assay precision (%CV) ranged from 5.58 to 13.89% and 5.23 to 13.36%, respectively, and intra- and inter-day accuracy (% deviation) ranged from -5.61 to 0.75% and -4.30 to 6.24%, respectively. A robust and sensitive LC-MS/MS assay for the high-throughput quantification of the antiretroviral drug dapivirine in human plasma was developed and validated following bioanalytical validation guidelines. The assay meets criteria for the analysis of samples from large research trials.
Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review
Current Drug Therapy
Background: Several clinical trials, as well as observational statistics, have exhibited that the advantages of antiretroviral [ARV] treatment for humans with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome HIV/AIDS exceed their risks. Therapeutic drug monitoring [TDM] plays a key role in optimization of ARV therapy. Determination of ARV’s in plasma, blood cells, and other biological matrices frequently requires separation techniques capable of high effectiveness, specific selectivity and high sensitivity. High-performance liquid chromatography [HPLC] coupled with ultraviolet [UV], Photodiode array detectors [PDA], Mass spectrophotometer [MS] detectors etc. are the important quantitative techniques used for the estimation of pharmaceuticals in biological samples. Objective: This review article is aimed to give an extensive outline of different bio-analytical techniques which have been reported for direct quantitation of ARV’s. This article aimed to establish an ef...
In vitro assessment of compounds for anti-HIV activity
Molecular Biotechnology, 1994
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