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Start Over Descriptor "Liquid chromatography tandem mass spectrometry" Journal analytical and bioanalytical chemistry
30 results on '"Liquid chromatography tandem mass spectrometry"'

29. Quantification of total dinutuximab concentrations in neuroblastoma patients with liquid chromatography tandem mass spectrometry

Author

Celina L. Szanto, Stefan Nierkens, Erik M. van Maarseveen, C. Erik Hack, Alwin D. R. Huitema, and Mohsin El Amrani

Subjects
Lysis, medicine.drug_class, Antineoplastic Agents, Peptide, Monoclonal antibody, 01 natural sciences, Biochemistry, Analytical Chemistry, Biopharmaceuticals, Neuroblastoma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Limit of Detection, Tandem Mass Spectrometry, Liquid chromatography–mass spectrometry, Quantification, medicine, Chemical Precipitation, Humans, Centrifugation, Amino Acid Sequence, Sodium dodecyl sulfate, Ammonium sulfate sample purification, Chromatography, High Pressure Liquid, chemistry.chemical_classification, Chromatography, 010401 analytical chemistry, Albumin, Antibodies, Monoclonal, Dinutuximab, Trypsin, 0104 chemical sciences, chemistry, 030220 oncology & carcinogenesis, Liquid chromatography tandem mass spectrometry, Therapeutic monoclonal antibody, Drug Monitoring, Research Paper, medicine.drug
Abstract

Neuroblastoma is one of the most commonly found solid tumors in children. The monoclonal antibody dinutuximab (DNX) targets the sialic acid-containing glycosphingolipid GD2 expressed on almost all neuroblastoma tumor cells and induces cell lysis. However, the expression of GD2 is not limited to tumor cells only, but is also present on central nerve tissue and peripheral nerve cells explaining dinutuximab toxicity. The most common adverse reactions are pain and discomfort, which may lead to discontinuation of the treatment. Furthermore, there is little to no data available on exposure and effect relationships of dinutuximab. We, therefore, developed an easy method in order to quantify dinutuximab levels in human plasma. Ammonium sulfate (AS) was used to precipitate all immunoglobulins (IgGs) in human plasma. After centrifugation, supernatant containing albumin was decanted and the precipitated IgG fraction was re-dissolved in a buffer containing 0.5% sodium dodecyl sulfate (SDS). Samples were then reduced, alkylated, and digested with trypsin. Finally, a signature peptide in complementarity determining region 1 of DNX heavy chain was quantified on LC-MS/MS using a stable isotopically labeled peptide as internal standard. AS purification efficiently removed 97.5% of the albumin fraction in the supernatant layer. The validation performed on DNX showed that within-run and between-run coefficients of variation (CV) for lower limit of quantification (LLOQ) were 5.5 and 1.4%, respectively. The overall CVs for quality control (QC) low, QC med, and QC high levels were 0.999). Selectivity, stability, and matrix effect were in concordance with EMA guidelines. In conclusion, a method to quantify DNX in human plasma was successfully developed. In addition, the high and robust process efficiency enabled the utilization of a stable isotopically labeled (SIL) peptide instead of SIL DNX, which was commercially unavailable. Graphical abstract.

Published
2018

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