Potential for Oxytetracycline Administration by Four Routes To Cause

Chapter 7

Potential for Oxytetracycline Administration by Four Routes To Cause Drug Residues in Milk of Lactating Cattle 1

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K. L. Anderson, W. A. Moats, J. E. Rushing, and J . O'Carroll

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Downloaded by NATL UNIV OF SINGAPORE on May 5, 2018 | https://pubs.acs.org Publication Date: May 5, 1996 | doi: 10.1021/bk-1996-0636.ch007

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Department of Food Animal and Equine Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606 Meat Science Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, M D 20705 Department of Food Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27606 2

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The potential for oxytetracycline (OTC) to cause milk residues above the FDA safe level was studied by administering OTC by 4 routes to lactating cows and measuring milk OTC concentrations over time using 2 analytical methods. Milk concentrations of OTC were determined from 18 lactating cows (6 cows per route) following administration of OTC by the intravenous (16.5 mg/kg once), intramuscular (11 mg/kg once), and intrauterine (2 grams once) routes. Milk was collected prior to and at twice daily milkings for 156 hours after OTC administration. Milk OTC was determined by an HPLC method and the Charm II test for tetracyclines. The intravenous and intramuscular routes were associated with considerable potential for violative milk residues. When OTC was administered orally at 5X the label dose for 3 days, milk OTC concentrations above the FDA safe level were not detected. Bulk milk samples from 5 dairies feeding oral chlortetracycline did not contain milk residues above the FDA safe level. Residues of tetracyclines have been reported in milk (1-2). This is a concern for the milk industry and regulatory officials. Other than for low-level administration by the oral route, tetracyclines are not approved for use in lactating cattle. However, tetracyclines are used by veterinarians in therapy of some serious diseases of lactating cattle under FDA extra-label use guidelines. Oxytetracycline (OTC) is one drug which is available and administered parenterally in such cases. Routes of administration of tetracyclines which may potentially lead to milk residues include intravenous (TV), intramuscular (IM), intrauterine (IU), oral, and others. Based upon reports of tetracycline residues above the FDA safe level of 30 ng/ml in milk, four routes of OTC administration were investigated. Data on the potential for residues following IV, IM, and IU administration have been published (3) and will 0097-6156/96/0636-0058$15.00/0 © 1996 American Chemical Society

Moats and Medina; Veterinary Drug Residues ACS Symposium Series; American Chemical Society: Washington, DC, 1996.

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Oxytetracycline Administration & Residues in Milk

ANDERSON ET AL.

only be summarized here. This communication will focus on investigation of the oral route of administration. Analytical Methods


HPLC Analysis of Milk. Milk OTC and chlortetracycline (CTC) concentrations were determined by the HPLC procedure of White et al (4) and Moats and HarikKhan (5). The limit of OTC quantitation was approximately 2 ng/ml (5). HPLC Analysis of Mineral Supplements. One gram of mineral concentrate was accurately weighed and transferred to a volumetricflaskwith a water rinse. Then 10 ml of IN HC1 and 10 ml of 0.2M tetramethyl ammonium chloride were added to the flask. After evolution of gas ceased, the contents of theflaskwere diluted to 100 ml, mixed thoroughly and allowed to stand 10 minutes. An aliquot of the contents of the flask wasfilteredthrough a plug of glass wool prior to analysis. The analytical procedure used a 4.6 χ 150 mm, 5 um particle-size, 100 angstrom pore diameter column (Polymer Laboratories PLRP-S). The HPLC mobile phase consisted of 0.02M H P0 , 0.0IM sodium decanesulfonate-acetonitrile (68+32). Theflowrate was 1 ml/min and detection was at 380 nm UV. HPLC standards for CTC and OTC (Sigma Chemical Co., St. Louis, MO) were prepared as stock solutions of 1 mg/ml with appropriate corrections for purity, when known, in 0.0 IN HC1. Working solutions of 100, 10 and 1 ug/ml were prepared in 0.01N HC1 and were stored at refrigerator temperature. 3

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Charm Π Competitive Assay for Tetracyclines. The Charm Π test (Charm Sciences Inc., Maiden, MA) for tetracyclines was performed as previously described (5). Milk samples from individual cows were centrifuged and skimmed prior to analysis. Concentrations were determinedfroma standard curve. When dilution was required, final concentrations in samples were determined by multiplying the derived concentration times the dilution factor. The limit of detection of the method was 5 ng/ml. Potential for Residues Following IV, IM and IU Administration Results of the investigation of potential for milk residues following IV, I M and IU administration of OTC (Liquamycin 100, Pfizer, Inc., New York, NY) have been published previously (5) and will only be summarized here. Values reported represent concentrations determined in pooled weigh jar milk samplesfrommachine milkings at approximately 12 hour intervals after treatment. The potential for OTC milk residues following IV, IM and IU administration is summarized in Table I. Intravenous (TV). Lactating Holstein cows (n=6) administered OTC IV at 16.5 mg/kg exhibited peak milk concentrations of OTC of approximately 3,700 to 4,200 ng/ml at the first milking after administration (Table I). Mean milk OTC concentrations rapidly declined and reached the FDA safe level at < 96 hours after administration. Assuming equal volumes of milkfromall herd cows, a single cow at

Moats and Medina; Veterinary Drug Residues ACS Symposium Series; American Chemical Society: Washington, DC, 1996.

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VETERINARY DRUG RESIDUES


peak concentrations could cause pooled herd milk to exceed the FDA safe level in herds of approximately 120-140 cows.

Table L Potential for OTC Residues Following a Single Administration by the IV, IM and IU Routes (n=6 per route, summarized from reference 3) Maximum OTC Milk Time for Mean OTC Administration Concentration at First Milk Concentrations to Route Dose Milking After TreatmentReach FDA Safe Level IV 16.5 mg/kg 3,700 to 4,200 ng/ml £ 96 hours IM 11 mg/kg 2,200 to 2,600 ng/ml £ 132 hours IU 2 gm/cow 186 to 192 ng/ml

Potential for Oxytetracycline Administration by Four Routes To Cause

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