A stability-indicating reversed-phase high performance liquid chromatography method for simultaneous assay of two corticosteroids and estimation of their related compounds in a pharmaceutical injectable formulation.
Betamethasone Sodium Phosphate and Betamethasone Acetate are the two corticosteroids active pharmaceutical ingredients (APIs) that are present in the injectable formulation, Celestone Chronodose(®) Injection. It is extremely challenging to develop a Quality Control friendly HPLC method to separate all the potential impurities and degradation products of the two APIs from each other using a single HPLC method. A novel stability-indicating reversed-phase HPLC (RP-HPLC) method using two oxo-cyclic organic modifiers in the mobile phase was developed and validated. This method can separate a total of 32 potential impurities and degradation products from the two APIs and also from each other. Peak symmetry and separation efficiency were enhanced by using two chaotropic agents (trifluoroacetic acid and potassium hexafluorophosphate) in the mobile phases of this method. The stability-indicating capability of this method has been demonstrated by analyzing aged and stressed degraded stability samples of the drug product. This method uses an ACE 3 C18 (15 cm × 4.6 mm) HPLC column. The method was validated per ICH guidelines and proved to be suitable for routine QC use.
Lu
Jun
J
Merck & Co. Inc., ACDS-SAS, Union, NJ 07083, USA. jun.lu2@merck.com
Wei
Yuchien
Y
Rustum
Abu M
AM
D001623:Betamethasone / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004340:Drug Contamination; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007267:Injections / Q000592:standards; D016014:Linear Models; D015203:Reproducibility of Results
C018230:betamethasone acetate phosphate; C028994:betamethasone sodium phosphate; D001623:Betamethasone