Product Number: M038022
English Name: Methylprednisolone Hydrogen Succinate EP Impurity F
English Alias: 4-(2-((6R,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethoxy)-4-oxobutanoic acid
CAS Number: 2376134-25-5
Molecular Formula: C₂₆H₃₄O₈
Molecular Weight: 474.54
As a European Pharmacopoeia (EP) impurity of Methylprednisolone Hydrogen Succinate, this compound has the following advantages:
Well-defined and distinct structure: Contains cyclopenta[a]phenanthrene steroid nucleus, dihydroxyl, ketone group, and succinic acid monoester chain, differing from the target compound in succinate linkage and esterification degree. Synergistic effects of multiple oxygen-containing groups (hydroxyl, ketone, ester, carboxyl) enable unique polarity and retention behavior, allowing accurate identification via HPLC and LC-MS as a specific impurity marker;
High stability and traceability: The conjugated system formed by steroid skeleton and multiple esters/carboxyls is stable under neutral conditions. As a by-product of incomplete succinylation, it directly reflects esterification efficiency, improving quality tracing accuracy;
High detection sensitivity: Strong UV absorption (240-260nm) from steroid conjugation, combined with characteristic mass response (m/z 475 [M+H]⁺), enables trace analysis (ppb level) via LC-MS, compatible with glucocorticoid ester derivative impurity systems.
Pharmaceutical quality control: Used as an EP reference standard to quantify Methylprednisolone Hydrogen Succinate EP Impurity F in APIs and formulations, ensuring residual esterification impurities meet EP standards;
Synthesis optimization: Optimizing succinic anhydride-methylprednisolone esterification (temperature, catalyst) by monitoring impurity levels to enhance target monoester selectivity;
Regulatory compliance: Validating impurity profile compliance with EP requirements to support EU market registration of methylprednisolone hydrogen succinate products.
Methylprednisolone Hydrogen Succinate, a glucocorticoid for inflammation and immune disorders, is synthesized via succinylation of methylprednisolone. Abnormal succinic anhydride binding or incomplete reaction may generate ester impurities like Methylprednisolone Hydrogen Succinate EP Impurity F. Its presence risks affecting solubility and bioavailability, making control critical for quality assurance per EP standards.
Current research focuses on:
Analytical method advancement: Developing UPLC-DAD assays with optimized mobile phase pH for baseline separation of impurity and target, achieving 0.5 ppb detection limits;
Esterification kinetics: Studying impurity formation under varying reaction conditions to clarify regioselectivity factors in methylprednisolone hydroxylation;
Stability studies: Evaluating impurity degradation under accelerated storage to guide formulation packaging design;
Pharmacopoeial method cross-validation: Verifying impurity quantification consistency across platforms to ensure EP compliance.