title: Detection of trace melamine in raw materials used for protein pharmaceutical manufacturing using surface-enhanced Raman spectroscopy (SERS) with gold nanoparticles.
abstract: Melamine, a nitrogen-rich molecule, was found as an adulterant in pet foods in 2007 in North America and in milk products in 2008 in China. These scandalous abuses of melamine have alarmed the biopharmaceutical industry and the FDA and alerted them to potential adulteration and contamination of melamine in raw materials used to make protein therapeutics. Highly sensitive analytical methods are needed to screen melamine adulteration and contamination in raw materials. We conducted surface-enhanced Raman spectroscopy (SERS) experiments to test trace melamine spiked in three raw materials commonly used for protein pharmaceutical formulation and purification, including sucrose, urea, and arginine, with a portable Raman device and gold nanoparticles. The detection limit of 10 ppb in raw material dissolved in 30:70% water/acetonitrile is equivalent to 0.5 ppm in solid raw material. It has excellent linearity in the concentration range measured. The cross-validation regression coefficient R(2) and the standard error of prediction (SEP) are 0.960 and 7.18 ppb, respectively, in sucrose. The R(2) and SEP are 0.958 and 9.15 ppb in urea. It has a relatively lower R(2) = 0.630 and a SEP of 35.0 ppb in arginine, which could be due to the competitive adsorption of arginine molecules to the surfaces of gold nanoparticles. The detection of melamine using the SERS technique is rapid (within 3 minutes), convenient, and requires no extraction procedure, offering an alternative method for screening melamine in raw materials at biopharmaceutical manufacture sites.
authors.affiliation: Department of Formulation and Analytical Resources, Amgen Inc., Thousand Oaks, California 91320, USA. zwen@amgen.com
authors.forename: Zai-Qing
authors.initials: ZQ
authors.lastname: Wen
authors.forename: Guiyang
authors.initials: G
authors.lastname: Li
authors.forename: Da
authors.initials: D
authors.lastname: Ren
mesh_terms: D004340:Drug Contamination; D006046:Gold / Q000737:chemistry*; D016014:Linear Models; D053768:Metal Nanoparticles / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014227:Triazines / Q000032:analysis*
chemical_list: D004364:Pharmaceutical Preparations; D014227:Triazines; D006046:Gold; C011907:melamine