Milk residue concentrations of ivermectin following pour-on administration to pregnant Holstein cows during different dry periods

This study aimed to compare ivermectin residue concentrations in milk following pour-on administration to Holstein cows at different stages of the dry period and to determine the necessary milk withdrawal period. Thirty dry cows were evenly divided into 3 groups based on estimated calving dates and received a single pour-on treatment of ivermectin at 0.5 mg/kg BW either 10, 20, or 30 d before these dates. Milk samples were collected 2 times daily for 7 consecutive days beginning on the second day after calving. The marker residue, 22,23-dihydroavermectin B1a, was measured using ultra-high-performance liquid chromatography tandem-MS/MS analysis, with the method showing strong correlation coefficients in the concentration range from 2.5 to 20 ng/mL. The limits of detection and quantification were 2 ng/mL and 2.5 ng/mL, respectively. The concentration-time data were analyzed using a noncompartmental model, and the milk withdrawal period was calculated with WTM 1.4 software (European Medicines Agency). Results showed that when cows received ivermectin more than 10 d before calving, residue concentrations in milk were undetectable or present only in trace amounts, well below China's maximum residue limit (MRL) for ivermectin (10 ng/mL). In contrast, cows treated within 10 d before calving had a milk elimination half-life of 3.8 d for 22,23-dihydroavermectin B1a, with a peak concentration in milk of 13.75 ± 8.12 ng/mL at 1.70 ± 1.68 d postcalving. Based on China's MRL and the observed results, no milk withdrawal period is required if the interval between pour-on administration and calving exceeds 10 d. However, a 4-d withdrawal period after calving is recommended when the interval is shorter. In contrast, in countries without an established MRL, the presence of any detectable ivermectin residue (even below 10 ng/mL) would be a violation.