Quantitation of terameprocol in human plasma by liquid chromatography-tandem mass spectrometry

Nicole M Anders; Carlos G Romo; Avelina Hemingway; Manmeet S Ahluwalia; Michelle A Rudek

doi:10.1016/j.jpba.2021.114525

Quantitation of terameprocol in human plasma by liquid chromatography-tandem mass spectrometry

J Pharm Biomed Anal. 2022 Feb 5:209:114525. doi: 10.1016/j.jpba.2021.114525. Epub 2021 Dec 7.

Authors

Nicole M Anders¹, Carlos G Romo², Avelina Hemingway³, Manmeet S Ahluwalia⁴, Michelle A Rudek⁵

Affiliations

¹ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.
² Department of Neurology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA; Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.
³ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
⁴ Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
⁵ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA; Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA. Electronic address: mrudek2@jhmi.edu.

Abstract

The global transcription inhibitor terameprocol is being evaluated clinically as an oral formulation to treat high-grade glioma. A sensitive, reliable method was developed to quantitate terameprocol using LC-MS/MS to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of terameprocol and the internal standard, Sorafenib-methyl-d3, was achieved with a Zorbax XDB C18 column (2.1 × 50 mm, 3.5 µm) and gradient elution over a 2-minute total analytical run time. A SCIEX 4500 or SCIEX 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for terameprocol detection. The assay range of 5-1000 ng/mL was demonstrated to be accurate (92.7-107.4%) and precise (CV ≤ 11.3%). A sample diluted 1:10 (v/v) was accurately quantitated. Terameprocol in plasma has been proven stable for at least 20 months when stored at -70 °C. The method was applied to the measurement of total plasma concentrations of terameprocol in a patient with a high-grade glioma receiving a 300 mg oral dose.

Keywords: Assay; Tandem mass spectrometry; Terameprocol; Validation.

MeSH terms

Chromatography, High Pressure Liquid
Chromatography, Liquid
Humans
Masoprocol / analogs & derivatives
Reproducibility of Results
Spectrometry, Mass, Electrospray Ionization*
Tandem Mass Spectrometry*

Substances

terameprocol
Masoprocol

Abstract

MeSH terms

Substances

Grants and funding