The determination of Sulfobutylether β-Cyclodextrin Sodium (SBECD) by LC-MS/MS and its Application in Remdesivir Pharmacokinetics Study for Pediatric Patients
SBECD (Captisol®) with an average degree of substitution of 6.5 sulfobutylether functional groups (SBE = 6.5), is a solubility enhancer for remdesivir (RDV) and a major component in Veklury, which was approved by FDA for the treatment of patients with COVID-19 over 12 years old and weighing over 40 kg who require hospitalization.
Highlights
A specific, robust, and reliable method to quantify SBECD by LC-MS/MS in human plasma was developed and validated.
The various degrees of substitution present in SBECD were evaluated, and the hexa-substituted species, SBE6, was selected for SBECD quantification.
Molecular (parent) Ion (Q1)/ Molecular (parent) Ion (Q3) of m/z 974.7/974.7 mass transition was used for quantitative analysis of SBE6.
The method was applied to monitor SBECD levels in pharmacokinetics study of SBECD for pediatric patients.
SBECD is cleared mainly by renal filtration, thus, potential accumulation of SBECD in the human body is a concern for patients dosed with Veklury with compromised renal function. An LC-MS/MS method was developed and validated for specific, accurate, and precise determination of SBECD concentrations in human plasma. In this method, the hexa-substituted species, SBE6, was selected for SBECD quantification, and the mass transition from its dicharged molecular ion [(M–2H)/ 2]2-, Molecular (parent) Ion (Q1)/Molecular (parent) Ion (Q3) of m/z 974.7/974.7, was selected for quantitative analysis of SBECD.
Captisol-G (SBE‐γ‐CD, SBE = 3) was chosen as the internal standard. With 25 µL of formic-acid-treated sample and with a calibration range of 10.0 to 1000 µg/mL, the method was validated with respect to pre-established criteria based on regulatory guidelines and was applied to determine SBECD levels in plasma samples collected from pediatric patients during RDV clinical studies.
Article information: Zhengdong Yang, Deqing Xiao, Kah Hiing John Ling, Thomas Tarnowski, Rita Humeniuk, Bryan Parmentier, Yu-Hui Ann Fu, Eric Johnson, Marsha L. Luna, Habibi Goudarzi, Quan Cheng, The Determination of Sulfobutylether β-Cyclodextrin Sodium (SBECD) by LC-MS/MS and its Application in Remdesivir Pharmacokinetics Study for Pediatric Patients, Journal of Pharmaceutical and Biomedical Analysis, 2022. https://doi.org/10.1016/j.jpba.2022.114646.