|FANASELLE, WENDY - Us Food & Drug Administration (FDA)|
|VAN DOREN, JANE - Us Food & Drug Administration (FDA)|
Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/4/2017
Publication Date: 1/4/2017
Citation: Shappell, N.W., Shelver, W.L., Lupton, S.J., Fanaselle, W., Van Doren, J.M., Hakk, H. 2017. Distribution of animal drugs among curd, whey, and milk protein fractions in spiked skim milk and whey. Journal of Agricultural and Food Chemistry. 65:938-949. doi:10.1021/acs.jafc.6b04258.
Interpretive Summary: In a previous study seven veterinary drugs, representing a broad range of antibiotics, anti-inflammatories, and anthelmintics were used to evaluate drug distribution into the milk fat and skim milk fractions of cow’s milk. This study continues that work, determining the distribution of the same drugs among curd, whey, casein proteins, and whey proteins. We hypothesized that drugs would distribute into the curd based on the drug’s fat solubility. The drugs that were highly fat soluble did indeed concentrate into curd to a greater degree than those with a lower fat solubility. By taking into consideration the charge or ionization state of the drug in milk, we were able to refine the correlation between distribution and solubility of the seven drugs significantly. The ultimate intent of this research is to develop a data-based model that can be used to predict the distribution of other drugs in milk and milk products. This information is needed to provide accurate estimates of human exposure to animal drug residues from consumption of milk products derived from drug residue-contaminated milk.
Technical Abstract: It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labelled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and thiabendazole were used to evaluate the distribution of animal drugs among rennet curd, whey, and protein fractions from skim cow milk. Our previous work reported the distribution of these same drugs between skim and fat fractions of milk. Drug distribution between curd and whey was significantly correlated (R2 = 0.70) to the drug’s lipophilicity (log P), with improved correlation using log D (R2 = 0.95). Distribution of drugs was concentration-independent over the range tested (20 – 2,000 nM). With the exception of thiabendazole and ivermectin, more drugs were associated with whey protein than casein on a nmol/mg protein basis (oxytetracycline experiment not performed). These results provide insights into the distribution of animal drug residues, if present in cow milk, among milk fractions, with possible extrapolation to milk products.