title: Impurity profiling of ibandronate sodium by HPLC-CAD.
abstract: The modern bisphosphonate drug ibandronate sodium, a challenging candidate for impurity profiling, was analyzed using high performance liquid chromatography (HPLC) combined with corona charged aerosol detection (CAD). Separation was achieved on a mixed mode column combining hydrophobic C18 and strong anion exchange retention mechanisms using a mass spectrometer compatible volatile mobile phase consisting of trifluoroacetic acid and acetonitrile while gradient elution was applied. The method was validated following the ICH guideline Q2(R1) and found suitable for the assessment of ibandronate's related substances. The observed CAD-response for all identified impurities was linear (R(2)>0.995) over a small concentration range (0.05-0.25) and a quantification limit of at least 0.03% was found. Four batches of two different manufacturers were tested by means of the method. None of the batches contained a single impurity above 0.05%. The major impurities of all batches were the synthesis by-products N-desmethyl- and N-despentyl ibandronate as well as N,N-dimethyl pamidronate.
authors.affiliation: University of Würzburg, Institute for Pharmacy and Food Chemistry, 97074 Würzburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wahl
authors.affiliation: University of Würzburg, Institute for Pharmacy and Food Chemistry, 97074 Würzburg, Germany. Electronic address: u.holzgrabe@pharmazie.uni-wuerzburg.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000336:Aerosols / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004164:Diphosphonates / Q000032:analysis* / Q000737:chemistry*; D004340:Drug Contamination; D006861:Hydrogen Peroxide / Q000737:chemistry; D000077557:Ibandronic Acid; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015203:Reproducibility of Results; D012964:Sodium / Q000737:chemistry; D012996:Solutions; D013696:Temperature
chemical_list: D000097:Acetonitriles; D000336:Aerosols; D004164:Diphosphonates; D012996:Solutions; D012964:Sodium; D006861:Hydrogen Peroxide; D000077557:Ibandronic Acid; C032159:acetonitrile
keywords: Bisphosphonates; Corona charged aerosol detector; Ibandronate; Pharmaceutical analysis