Macrocyclic lactone residues in milk: chemical stability and pattern of residual concentrations during milk processing

IMPERIALE, F.; PIS, A.; SALLOVITZ, J.; LIFSCHITZ, A.; LANUSSE, C.

Torino, Italia

Congreso; 10th International Congress of the European Association for Veterinary Pharmacology and Toxicology; 2006

European Association for Veterinary Pharmacology and Toxicology and Faculty of Veterinary Medicine, University of Turin

Introduction The presence of drug residues in milk is a problem that has been focused mainly towards antimicrobial agents due to their impact on milk industrial processing. Nevertheless, it is necessary to know the consequences that the residues of other substances, used extensively in dairy animals, could have on the processes of elaboration of milk products. The presence of antiparasitic drug residues is usually refers to drug concentrations in raw tissues (liver, muscle, fat) but the effect of different food processing methods (pasteurization, cooking, ripening, etc.) on the chemical stability and persistence of drug residues in milk and dairy products is unknown. Ivermectin (IVM), moxidectin (MXD) and eprinomectin (EPM) are broad-spectrum macrocyclic lactone (ML) antiparasitic drugs extensively used in food-producing animals (1). The pattern of milk residue excretion for different ML compounds in dairy sheep has been recently determined in our laboratory (2). As a follow up, the current trial addressed the evaluation of the chemical stability of residual concentrations of IVM, MXD and EPM in milk and to determine the comparative pattern of residues in whey, curd and cheese prepared from milk from dairy sheep treated with those ML compounds. Materials and Methods IVM (0.25-10 ng.ml-1), EPM (0.1-5 ng.ml-1) and MXD (10-200 ng.ml-1) was added to drug-free milk samples collected from untreated lactating ewes. Milk samples with drug added were heated at 65ºC for 30min (pasteurization) or at 75ºC for 15s (high temperature short time pasteurization). IVM, MXD and EPM concentrations were measured prior and after the heating process as described below. Semi-hard cheeses were elaborated with pooled milk collected daily (up to 25 days post-treatment) from ewes treated with either IVM, MXD (200 mg.kg-1 s.c.) or EPM (500 mg.kg-1 pour-on). Drug residues in curd and whey collected during cheese-making were measured. IVM, MXD and EPM concentrations were measured in raw milk, heated milk and in dairy products (whey, curd and cheese) using an HPLC methodology previously reported (3). Additionally, the acidity, dry matter, fat content and total nitrogen in milk collected from untreated and ML treated-dairy sheep before milk processing were determined. Results No significant changes in the IVM, MXD and EPM residue profiles were observed after either thermal treatment (65ºC, 30 min or 75ºC, 15 s), the variation observed in heated milk residual concentration being within the range of the analytical method. The presence of ML residues affected neither the acidity value, nor the dry matter, fat or total nitrogen content of raw milk. High residual concentrations of the parent compounds were found in curd. The ML residue profiles measured in curd were significantly higher than those detected in the milk collected from treated sheep. The ratios between drug residue concentrations measured in curd and milk were: 2.8 ± 0.23 (IVM), 2.4 ± 0.17 (MXD) and 3.4 ± 0.24 (EPM). A lower proportion of these lipophilic analytes ended in whey due to a high water content of this dairy product. The highest residual concentrations of these ML were detected in ripened cheese. The ratios between drug concentrations in semi-hard cheese and milk were: 3.3 ± 0.45 (IVM), 3.4 ± 0.38 (MXD) and 5.1 ± 0.65 (EPM). Weight reduction in the cheese due to water loss during ripening was observed. This water loss and the subsequent increment of total solid and fat content in ripened cheese may have accounted for the high residual concentrations of ML found after 40 days of maturation. Linear correlations between percentages of water loss, total solid, fat contents and drug residual concentrations during cheese maturation were observed (r >0.90). Discussion IVM, MXD and EPM residues in sheep milk were chemically stable after exposure to pasteurization temperatures, which agrees with results previously reported for IVM in heated milk (4). The total amount of drug residues recovered from milk was markedly lower for EPM compared to both IVM and MXD. However, the concentration ratios cheese/milk were similar for the three ML compounds. The highest residual concentrations were consistently recovered from curd and cheese, in line with their higher fat and total solid contents compared to the milk. The outcome of the work presented here is complementary to the available information (2, 5, 6) and demonstrates that the presence of ML residual concentrations does not affect milk physicochemical features of milk. IVM, MXD and EPM residual concentrations persist unchanged during milk processing reaching concentration levels three to five-fold higher in ripened cheese than in milk. References 1. Baynes et al. (2000) JAVMA; 217: 668-671. 2. Imperiale et al. (2004) J Dairy Res; 71: 427-433. 3. Imperiale et al. (2004) J Agric Food Chem; 52: 6205-6211. 4. Cerkvenik et al. (2001) Eur Food Res Technol; 213: 72-76. 5. Cerkvenik et al. (2004) J Dairy Res; 71: 39-45. 6. Anastasio et al. (2005) J Food Prot; 68: 1097-1101.