The occurrence, concentrations, and variables associated with tetracycline, polyether ionophore, and anthelmintic residues in the livers of chickens sold in the informal market in South Africa were determined. Ultrahigh-performance liquid chromatography–tandem mass spectrometry was used to simultaneously analyze for four tetracyclines, five polyether ionophores, and six anthelmintic residues. The study determined the presence of residues in liver samples at both the limit of quantifications (LOQ) and concentrations over the maximum residue limit (MRL), i.e., noncompliant. Doxycycline (tetracycline group) was detected in 24 (24.5%) of 98 chicken livers, and 15 (15.3%) of the 98 were noncompliant. Mean ± standard deviation (SD) concentrations of 919.04 ± 1,081.30 ppb (LOQ) and 1,410.57 ± 108.89 ppb (MRL) were obtained. Maduramicin was detected in 27 (27.6%) of 98 chicken livers, and 19 (19.4%) of 98 were noncompliant. The mean ± SD for LOQ was 117.96 ± 84.56 ppb, and MRL was 153.21 ± 76.29 ppb. The concentrations of residues of doxycycline and maduramicin in chicken livers varied significantly across townships. Lasalocid was found in 31 (31.6%) of 98 samples, of which 5 (5.1%) had concentrations above the MRL. The mean ± SD concentration of lasalocid was 62.90 ± 170.84 ppb for samples in which lasalocid was quantified and 310.16 ± 356.68 ppb for noncompliant samples. Detectable concentrations of praziquantel, closantel, and rafoxanide (anthelmintics) residues were found in 3 (3.1%), 1 (1.0%), and 2 (2.0%) of 98 chicken livers, respectively. The presence of residues of three classes of veterinary drugs in chicken livers poses food safety implications to consumers and indicates a need for enhanced regulatory enforcement in controlling these drugs in South Africa.

  • Tetracyclines, polyether ionophores, and anthelmintics were assayed in chicken livers.

  • Noncompliant concentrations of doxycycline residues were detected in 15.3% of liver samples.

  • Noncompliant concentrations of maduramicin (9.4%) and lasalocid (5.1%) were detected.

  • Doxycycline, maduramicin, and lasalocid residues in chicken liver pose a food safety hazard.

  • Residues indicate noncompliant use of veterinary drugs in the informal poultry sector.

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