title: HPLC-UV method development and validation for the determination of low level formaldehyde in a drug substance.
abstract: A reversed-phase high-performance liquid chromatographic method (HPLC) with diode-array detection is developed and validated for the quantitative determination of formaldehyde in a drug substance. Formaldehyde (HCHO) is reacted with 2,4-dinitrophenylhydrazine (DNPH) to form a Schiff base (HCHO-DNPH derivatization product), which has an absorbing maximum (lambda max) at 360 nm. The HPLC method employs a C8, 3-microm particle size analytical column (150 mm x 4.6 mm), 15-microL injection volume, column temperature controlled at 30 degrees C, detection at 360 nm, and a water-acetonitrile (55:45, v/v) mobile phase at a flow rate of 1 mL/min. These conditions resolve the HCHO-DNPH product from unreacted DNPH, the drug substance and related impurities, as well as diluent peaks within 20 min. The retention time of the HCHO-DNPH product is approximately 6.4 min. The method is linear, accurate in the specified range (0.33-333 ppm), and robust based on analyte (HCHO-DNPH derivatization product) stability in standard and sample. Detection limit is 0.03 ng (0.1 ppm).
authors.affiliation: Analytical Sciences Department, Research and Development Center, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
authors.forename: A
authors.initials: A
authors.lastname: Soman
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.forename: Q
authors.initials: Q
authors.lastname: Chan Li
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005557:Formaldehyde / Q000032:analysis*; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D005557:Formaldehyde