title: Screening of heparin API by near infrared reflectance and Raman spectroscopy.
abstract: Near infrared (NIR) reflectance and laser Raman spectra for a set of 69 heparin powder samples obtained from several foreign and domestic suppliers were measured. Both the NIR and Raman spectra of individual heparin API powder samples were correlated with sample compositions determined from response corrected relative peak areas of the capillary electropherograms of the samples using a partial least squares (PLS) regression model. Twenty-eight sample spectra were used to develop PLS models for the three major sample components; heparin, oversulfated chondroitin sulfate (OSCS) and glycosaminoglycans (GAGs). The PLS models were then used to successfully predict the compositions of 41 additional heparin samples. The success of these rapid, nondestructive technologies to identify contamination of heparin with OSCS demonstrates the potential of spectroscopy and chemometrics for screening of processed raw materials. These technologies are meant for screening purposes and not meant to replace either of the methods (capillary electrophoresis and NMR) currently required by USP and FDA.
authors.affiliation: Division of Pharmaceutical Analysis, Food and Drug Administration, Center for Drug Evaluation and Research, St Louis, Missouri 63101, USA. john.spencer@fda.hhs.gov
authors.forename: John A
authors.initials: JA
authors.lastname: Spencer
authors.forename: John F
authors.initials: JF
authors.lastname: Kauffman
authors.forename: John C
authors.initials: JC
authors.lastname: Reepmeyer
authors.forename: Connie M
authors.initials: CM
authors.lastname: Gryniewicz
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Duckhee Y
authors.initials: DY
authors.lastname: Toler
authors.forename: Lucinda F
authors.initials: LF
authors.lastname: Buhse
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Westenberger
mesh_terms: D000925:Anticoagulants / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002681:China; D002809:Chondroitin Sulfates / Q000032:analysis; D004340:Drug Contamination; D004345:Drug Industry; D019075:Electrophoresis, Capillary; D006025:Glycosaminoglycans / Q000032:analysis; D006493:Heparin / Q000737:chemistry*; D016018:Least-Squares Analysis; D011208:Powders; D012015:Reference Standards; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared; D013059:Spectrum Analysis, Raman; D014481:United States
chemical_list: D000925:Anticoagulants; D006025:Glycosaminoglycans; D011208:Powders; D006493:Heparin; D002809:Chondroitin Sulfates