An LC‐MS‐MS method for quantitative determination of maraviroc (UK‐427,857) in human plasma, urine and cerebrospinal fluid

Brewer, Ed; Felix, Tonya; Clarke, Phil; Edgington, A.; Muirhead, David

doi:10.1002/bmc.1442

Cited by 14 publications

(12 citation statements)

References 2 publications

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“…Further, according to the Department of Health and Human Services, Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, the suggested minimum target trough concentration for maraviroc in ART-experienced patients with drug resistance is >50 ng/ml [16]. Previous approaches for the detection and quantification of maraviroc from biological matrices include high-performance liquid chromatography with ultra violet detection (HPLC-UV) and liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analyses [17-22]. Many of these assays have lower limits of quantitation (LLOQ) ranging from 1 to 11 ng/ml, which may not be sufficient for monitoring systemic plasma drug concentrations following topical administration.…”

Section: Introductionmentioning

confidence: 99%

Development and bioanalytical validation of a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist maraviroc in human plasma

Emory¹,

Seserko²,

Marzinke³

2014

Clinica Chimica Acta

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Background Maraviroc is a CCR5 antagonist that has been utilized as a viral entry inhibitor in the management of HIV-1. Current clinical trials are pursuing maraviroc drug efficacy in both oral and topical formulations. Therefore, in order to fully understand drug pharmacokinetics, a sensitive method is required to quantify plasma drug concentrations. Methods Maraviroc-spiked plasma was combined with acetonitrile containing an isotopically-labeled internal standard, and following protein precipitation, samples were evaporated to dryness and reconstituted for liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis. Chromatographic separation was achieved on a Waters BEH C8, 50 × 2.1 mm UPLC column, with a 1.7 μm particle size and the eluent was analyzed using an API 4000 mass analyzer in selected reaction monitoring mode. The method was validated as per FDA Bioanalytical Method Validation guidelines. Results The analytical measuring range of the LC-MS/MS method is 0.5-1000 ng/ml. Calibration curves were generated using weighted 1/x2 quadratic regression. Inter-and intra-assay precision was ≤ 5.38% and ≤ 5.98%, respectively; inter-and intra-assay accuracy (%DEV) was ≤ 10.2% and ≤ 8.44%, respectively. Additional studies illustrated similar matrix effects between maraviroc and its internal standard, and that maraviroc is stable under a variety of conditions. Method comparison studies with a reference LC-MS/MS method show a slope of 0.948 with a Spearman coefficient of 0.98. Conclusions Based on the validation metrics, we have generated a sensitive and automated LC-MS/MS method for maraviroc quantification in human plasma.

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Section: Introductionmentioning

confidence: 99%

Development and bioanalytical validation of a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist maraviroc in human plasma

Emory¹,

Seserko²,

Marzinke³

2014

Clinica Chimica Acta

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“…Fayet et al validated a LC-MS/MS assay for ETR, MVC and RAL, in addition to darunavir, in human plasma[16]. Other LC-MS/MS assays have been published for quantification of each drug alone, including ETR in human plasma and peripheral blood mononuclear cells and rat plasma[17, 18], MVC in human plasma, urine and cerebrospinal fluid[19], and RAL in human plasma and peripheral blood mononuclear cells[20, 21]. The combination of ETR, MVC and RAL has also been quantified using LC-MS/MS in human plasma in addition to a combination of eight other relevant antiretroviral drugs[22].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous measurement of etravirine, maraviroc and raltegravir in pigtail macaque plasma, vaginal secretions and vaginal tissue using a LC–MS/MS assay

Blakney

Jiang

Whittington

et al. 2016

Journal of Chromatography B

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Etravirine (ETR), maraviroc (MVC) and raltegravir (RAL) are promising antiretroviral drugs being used in HIV treatment and may be interesting for prevention applications such as oral or topical pre-exposure prophylaxis. Here we describe a sensitive and accurate method for the simultaneous detection of ETR, MVC and RAL from pigtail macaque plasma, vaginal secretions, and vaginal tissue. This method is characterized by a straightforward precipitation extraction method, a limit of quantification <0.5 ng mL−1 for all three antiretrovirals bolstered by a corresponding internal standard for each drug analyte, and short run time. Quantification is performed using positive ion electrospray triple quadrupole mass spectrometry. This method was validated over clinically relevant ranges for the three ARV drugs in all three matrices: 0.1–100 ng mL−1 for ETR, 0.05–100 ng mL−1 for MVC and 1–100 ng mL−1 for RAL. Our method is accurate and precise, with measured mean inter-assay precision (%CV) and accuracy (% bias) of 5.08% and 1.96%, respectively, while the mean intra-assay precision and accuracy were 3.44% and 1.08 %. The overall post-extraction recovery for ETR, MVC and RAL was >94% in all cases. We also show that extracted biological samples are stable after storage at room temperature or 4 °C and after three freeze/thaw cycles. This is the first analytical method capable of quantifying ETR, MVC and RAL in biological matrices relevant for pre-clinical testing of oral or topical HIV prevention methods in pigtailed macaques.

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“…Plasma samples were analyzed for MVC (Tandem Labs, West Trenton, NJ),10 and for BOC and TVR (Covance Bioanalytical Services, Shanghai, China), using a solid-phase extraction and a validated high-performance liquid chromatography/dual mass spectrometry assay.…”

Section: Methodsmentioning

confidence: 99%

The Effects of Boceprevir and Telaprevir on the Pharmacokinetics of Maraviroc

Vourvahis

Plotka

Kantaridis

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective:To evaluate the effects of boceprevir (BOC) and telaprevir (TVR) on the pharmacokinetics (PK) of maraviroc (MVC) in healthy volunteers.Methods:In this open-label, fixed-sequence study, 14 volunteers received MVC 150 mg twice daily alone for 5 days (period 1), followed by MVC + BOC 800 mg 3 times daily and MVC + TVR 750 mg 3 times daily, each for 10 days in periods 2 and 3, respectively, with a ≥10-day wash-out. PK was analyzed on day 5 of period 1 and day 10 of periods 2 and 3. Safety was also assessed.Results:Ratios of the adjusted geometric means (90% confidence intervals) for MVC area under the curve from predose to 12 hours, maximum plasma concentration, and plasma concentration at 12 hours were 3.02 (2.53 to 3.59), 3.33 (2.54 to 4.36), and 2.78 (2.40 to 3.23), respectively, for MVC + BOC versus MVC alone, and 9.49 (7.94 to 11.34), 7.81 (5.92 to 10.32), and 10.17 (8.73 to 11.85), respectively, for MVC + TVR versus MVC alone. PK profiles for MVC + BOC or TVR were consistent with historic values for BOC and TVR monotherapy. Adverse event incidence was higher with MVC + BOC and MVC + TVR versus MVC alone. Dysgeusia (50%) and pruritus (29%) occurred most commonly with MVC + BOC, and fatigue (46%) and headache (31%) with MVC + TVR. There were no serious adverse events.Conclusions:MVC exposures were significantly increased with BOC or TVR, therefore MVC should be dosed at 150 mg twice daily when coadministered with these newly approved hepatitis C protease inhibitors. No dose adjustment for BOC or TVR is warranted with MVC. MVC + BOC or TVR was generally well tolerated with no unexpected safety findings.

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An LC‐MS‐MS method for quantitative determination of maraviroc (UK‐427,857) in human plasma, urine and cerebrospinal fluid

Cited by 14 publications

References 2 publications

Development and bioanalytical validation of a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist maraviroc in human plasma

Development and bioanalytical validation of a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist maraviroc in human plasma

Simultaneous measurement of etravirine, maraviroc and raltegravir in pigtail macaque plasma, vaginal secretions and vaginal tissue using a LC–MS/MS assay

The Effects of Boceprevir and Telaprevir on the Pharmacokinetics of Maraviroc

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