Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS

Hummert, Pamela; Manohar, Madhuri; Aung, Wutyi; Marzinke, Mark A.

doi:10.1373/jalm.2016.020511

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…Further, recovery efficiency (%RE) was defined as the ratio of the peak area of the preextracted samples to that of the postextracted samples, multiplied by 100, and processing efficiency (%PE) was defined as the ratio of the peak area of the preextracted samples to that of the unextracted samples, multiplied by 100. The approach used for the quantitative assessment of matrix effects is aligned with experiments described by Matuszewski et al, and more details describing these experiments may also be found in previous publications by our group (14,15).…”

Section: Methods Validationmentioning

confidence: 99%

An Ultraperformance LC-MS/MS Method for the Quantification of the Antimalarial Atovaquone in Plasma

Chambliss

Parsons

Marzinke

2017

The Journal of Applied Laboratory Medicine

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Background: A primary modality in the treatment and prevention of malaria is the administration of antimalarial agents. Atovaquone (ATQ) has been used in single-drug and multidrug antimalarial applications; however, studies have demonstrated high interindividual drug variability. With the scarcity of analytical methodologies available in the literature, we have developed and optimized a rapid, ultraperformance (UP) LC-MS/MS method for the quantification of ATQ in human plasma. Methods: ATQ was extracted from 25 μL K 2 -EDTA human plasma via protein precipitation with acetonitrile. Sample solutions were separated on a Synergi 2.5-μm Polar-RP 100A (100 × 2 mm) column. ATQ and its internal standard were detected over 1.3 min on an API 4000 mass analyzer using an electrospray ionization source operated in negative ionization and selected reaction monitoring modes. The method was validated in accordance with the Food and Drug Administration (FDA) Guidance for Industry: Bioanalytical Method Validation recommendations. Results: Owing to pharmacokinetic parameters associated with ATQ, 2 calibration curves were generated to quantify the drug across a dynamic concentration range. Two standard curves were established ranging from 250 to 5000 ng/mL and 5000 to 50000 ng/mL, respectively. QC levels for both lower and higher concentration ranges prepared at low (750 ng/mL, 12000 ng/mL), mid (2000 ng/mL, 22500 ng/mL), and high (4250 ng/mL, 42500 ng/mL) concentrations yielded interassay precision ≤9.1% and accuracy ≤±9.4%. Dilutional, stability, and matrix effects studies were also performed, and results were within acceptability limits. Conclusions: This work describes the development and analytical evaluation of a UPLC-MS/MS method for ATQ quantification in plasma. The described method is sufficiently sensitive for ATQ quantification in plasma to support preclinical and clinical trials.

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Section: Methods Validationmentioning

confidence: 99%

An Ultraperformance LC-MS/MS Method for the Quantification of the Antimalarial Atovaquone in Plasma

Chambliss

Parsons

Marzinke

2017

The Journal of Applied Laboratory Medicine

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“…We measured all analytes using previously described and validated liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) methods. 28,[33][34][35] Assay lower limits of quantification (LLOQ) were as follows: plasma MPA 200 pg/mL; plasma TFV 1 ng/mL; plasma FTC 5 ng/mL; cervical tissue homogenate TFV 0.05 ng/sample; cervical tissue homogenate FTC #0.25 ng/sample; urine TFV 50 ng/mL; urine FTC 50 ng/mL; TFV-DP in PBMC and cervical tissue homogenate 50 fmol/sample for an earlier version of the assay, and transitioned to 5 fmol/sample using an upgraded LC-MS/MS method. Adjusting for cell number or biopsy mass, median LLOQs are PBMC TFV-DP 5 fmol/ million cells, tissue TFV-DP 5 fmol/mg (based on the less sensitive of the methods), tissue TFV 0.006 ng/mg, and tissue FTC #0.03 ng/mg.…”

Section: Drug Concentration Analysismentioning

confidence: 99%

“…Two of these 14 dropped out before visit 2. The remaining 12 women had median (IQR) age of 34 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37) years and weighed 90 (78-101) kg, and 9, 2, and 1 participant self-identified as of African, European, and Asian ancestry, respectively. One African ancestry participant identified as Hispanic.…”

Section: Demographics and Clinical Characteristicsmentioning

confidence: 99%

Interaction of Depot Medroxyprogesterone Acetate and Tenofovir Disoproxil Fumarate/Emtricitabine on Peripheral Blood Mononuclear Cells and Cervical Tissue Susceptibility to HIV Infection and Pharmacokinetics

Coleman

Diniz

Fuchs

et al. 2023

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics.Methods: Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4-and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIV BaL ), endocrine, immune cell phenotyping, and renal function.Results: Compared with baseline, F/TDF (6 DMPA) significantly decreased both %R5-and X4-infected CD4 T cells and F/ TDF + DMPA decreased cervical explant p24 (all P , 0.05). The %R5-and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions.Conclusions: F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.

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“…Recovery was evaluated by comparing the preextracted samples to postextracted samples. Matrix effect was evaluated by comparing postextracted samples to unextracted samples (17,18):…”

Section: Recovery and Matrix Effectmentioning

confidence: 99%

A Rapid High-Performance LC-MS/MS Method for Therapeutic Drug Monitoring of Voriconazole, Posaconazole, Fluconazole, and Itraconazole in Human Serum

Xiao

Pattengale

et al. 2017

The Journal of Applied Laboratory Medicine

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Background: To achieve therapeutic efficacy and prevent toxicity simultaneously, therapeutic drug monitoring has been increasingly adopted for antifungal agents with narrow therapeutic indexes. We herein report the development and validation of an accurate, simple, fast, and cost-effective clinical test with high-performance LC-MS/MS to simultaneously quantify voriconazole, posaconazole, fluconazole, and itraconazole in human serum. Methods: Mixed with extraction solution and internal standard, 100 μL serum samples were centrifuged for protein precipitation. Diluted supernatant was injected onto a Phenomenex ® Luna C8 (2) 50 × 2 mm (3 μm) column and was analyzed with a Prominence Shimadzu high-performance liquid chromatography (HPLC) system coupled with a SCIEX QTRAP 4000 mass spectrometer in a positive ionization mode with multiple reaction monitoring. The total analytical run time was 3 min. Results: The assay is linear for voricoanzole (0.01-10 μg/mL), posaconazole (0.02-40 μg/mL), fluconazole (0.2-200 μg/mL), and itraconazole (0.02-20 μg/mL). The intraday CVs ranged from 1.9% to 3.8% (n = 20); the interday CVs ranged from 2.7% to 5.4% (n = 20). Method comparison study (n = 39 or 40) demonstrated good correlation with reference laboratories (R >0.99) with average biases ranging from −7.2% to 17.5%. The recoveries for each analyte were above 90%, and matrix effects ranged from 95% to 112%. Conclusions: The method is acceptable for routine therapeutic drug monitoring of these antifungal agents in clinical laboratories for better therapeutic outcome. IMPACT STATEMENT The method is being used for therapeutic drug monitoring of commonly used antifungal agents (voriconazole, posaconazole, itraconazole, and fluconazole) for life-threatening fungal infections (e.g., Aspergillus and Candida) and prophylaxis of these infections in immunocompromised patients for better therapeutic outcome. The simple sample preparation and reduced analytical run time (3 min) can dramatically reduce turnaround time and further reduce hospital stay. The method simultaneously measures 4 antifungal agents. It can be easily scaled up to a 96-well format and can be adopted with large sample volume.

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Rapid Quantification of Medroxyprogesterone Acetate (MPA) in Human Plasma by LC-MS/MS

Cited by 5 publications

References 19 publications

An Ultraperformance LC-MS/MS Method for the Quantification of the Antimalarial Atovaquone in Plasma

An Ultraperformance LC-MS/MS Method for the Quantification of the Antimalarial Atovaquone in Plasma

Interaction of Depot Medroxyprogesterone Acetate and Tenofovir Disoproxil Fumarate/Emtricitabine on Peripheral Blood Mononuclear Cells and Cervical Tissue Susceptibility to HIV Infection and Pharmacokinetics

A Rapid High-Performance LC-MS/MS Method for Therapeutic Drug Monitoring of Voriconazole, Posaconazole, Fluconazole, and Itraconazole in Human Serum

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