Moxidectin residues in lamb tissues: Development and validation of analytical method by UHPLC-MS/MS (original) (raw)
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Journal of the Brazilian Chemical Society, 2016
The widespread use of moxidectin (MOX), a parasiticide used in the sheep breeding, has induced the parasite resistance in Brazilian farms. As a consequence, the farmers often increase the dose and frequency of drug utilization, and disregards safety of meat or milk. In order to establish adequate therapeutic treatment it is necessary to know the pharmacokinetics of the drug in the animal's body. Thus, high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for the determination of MOX in serum lamb. Serum samples were treated with acetonitrile to precipitate proteins. A clean up by dispersive extraction in solid phase (SPE-d), using primary/secondary amine (PSA) and C18 sorbents, followed by freezing was performed. Method validation presented precision (coefficient of variation) and accuracy (recovery%) between 1.7-6.7 and 80.0-107.3%, respectively. The limit of quantification (LOQ) of the method was 2.0 ng mL-1 and a linear response was obtained over a range of 2.0 to 100 ng mL-1. This method was successfully applied to the determination of MOX in serum from suffolk lamb to evaluate the pharmacokinetic profile.
Tissue residue depletion of moxidectin in lambs (Ovis aries) following subcutaneous administration
Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment, 2018
To date, a tissue depletion study of moxidectin (MOX) in lambs is not available. Thus, considering that lamb meat is of great commercial interest in the world, the aim of the present study was to determine the residue levels of MOX in lamb target-tissues (muscle, liver, kidney, and fat) and subsequently calculate the MOX withdrawal period. For this purpose, the target-tissues were analysed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Method validation was performed based on Commission Decision 2002/657/EC and VICH GL49. To quantify the analyte, matrix-matched analytical curves were constructed with spiked blank tissues. The limits of detection and quantitation were 1.5 ng g and 5 ng g, respectively for all matrices. The linearity, decision limit, detection capability accuracy, and inter- and intra-day precision of the method are reported. The lambs were treated with a single subcutaneous (s.c.) dose of 0.2 mg MOX kg body weight (bw), and we...
Moxidectin residues in tissues of lambs submitted to three endoparasite control programs
Research in veterinary science, 2017
The indiscriminate and continuous use of anthelmintic drugs has promoted the selection of resistant parasites population, the presence of drug residues in food products, and heavy environmental contamination. The aim of the present study was to determine the presence of antiparasitic drug residues in 42-days old lamb serum and tissues, submitted to three endoparasite control programs: preventive treatment (PT) using moxidectin (MOX) at every 28days; selective treatment (FEC) using MOX when fecal egg count was greater than or equal to 700; and selective treatment (FMC), using MOX when FAMACHA/FMC score was 3 and above. For this purpose, MOX residues were quantified in serum, muscle, fat, liver and kidney. Lambs were slaughtered when reaching 30kg of body weight, and after a 28-day MOX withdrawal period. Before slaughter, blood was collected to determine the concentration of MOX in serum. Tissues and organ samples were collected at slaughter. The quantitation of MOX residues was perfo...
Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: quercetin
Veterinary Parasitology, 2003
Moxidectin is an antiparasitic drug widely used in cattle, sheep and companion animals. Due to the involvement of P-glycoprotein (P-gp) and cytochrome P450 3A in the metabolism of moxidectin, we studied the influence of various P-gp interfering agents (ivermectin, quercetin and ketoconazole) on the metabolism of 14 C moxidectin in cultured rat hepatocytes over 72 h. This in vitro study allowed selection of compounds which are able to increase the moxidectin bioavailability in lambs. From this, the modulation of moxidectin pharmacokinetics in plasma of lambs was studied after co-administration of 0.2 mg kg −1 moxidectin (subcutaneously (SC)) and 0.2 mg kg −1 ivermectin (SC), or 10 mg kg −1 quercetin (SC), or 10 mg kg −1 ketoconazole (orally). Ivermectin and quercetin increased significantly the quantity of 14 C moxidectin in the rat hepatocytes. Ketoconazole co-administration led to a higher concentration of moxidectin in the rat hepatocytes. In vivo, only quercetin was able to modify the pharmacokinetics of moxidectin in plasma of lambs by increasing significantly the area under the plasma concentration-time curve. This study allowed the use of a natural agent, quercetin, to improve the bioavailability of moxidectin.
Journal of the Brazilian Chemical Society, 2016
A fast and sensitive method using high performance liquid chromatography-fluorescence detection (HPLC-FD) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the determination of avermectins residues in ovine muscle samples. QuEChERS (quick, easy, cheap, effective, rugged and safe) sample preparation based on acetonitrile extraction followed by partitioning with NaCl and Na 2 SO 4 and dispersive solid-phase extraction (d-SPE) clean-up with C18 was applied. Na 2 SO 4 was used instead of MgSO 4 due to lower amounts of co-extractives in the final extract. The procedure was validated according to the Commission Decision 2002/657/EC. The method showed determination coefficients (r 2) higher than 0.99, recoveries between 93.2 and 124.3% for spike levels between 0.5 and 2.0 times the maximum residues limit (MRL) values. The repeatability and intermediate precision RSD values ranged from 1 to 19%. Decision limits (CCα) and detection capabilities (CCβ) ranged from 10.7 to 59.4 μg kg-1 and 11.4 to 68.8 μg kg-1 , respectively. Method performance was successfully evaluated by analyzing real samples and proficiency test with a z-score in the range of ±1.
Journal of Pharmaceutical and Biomedical Analysis, 2002
A sensitive and selective high-performance liquid chromatography (HPLC) method is presented for the analysis of moxidectin in human plasma. Solid phase extraction using Oasis ® HLB cartridges is used for sample preparation. The fluorescent derivative is obtained by a dehydrative reaction with trifluoroacetic anhydride and N-methylimidazole. Separation is achieved on a Bondapak C 18 reversed-phase column with a mobile phase composed of tetrahydrafuranacetonitrile-water (40:40:20, v/v/v). Detection is by fluorescence, with excitation at 365 nm and emission at 475 nm. The retention times of moxidectin and internal standard, ivermectin are approximately 10.7 and 18.6 min, respectively. The assay is linear over the concentration range 0.2-1000 ng/ml for moxidectin in human plasma (r =0.9999, weighted by 1/concentration). Recoveries at concentrations 0.2, 400, 1000 ng/ml are 94, 75, and 71%, respectively. The analysis of quality control (QC) samples for moxidectin (0.2, 400, and 1000 ng/ml) demonstrates excellent precision with relative standard deviations of 11.9, 5.7, and 2.7%, respectively (n= 6). The method is accurate with all intra-(n=6) and inter-day (n=18) mean concentrations within (5.0%) from nominal at all QC sample concentrations. Moxidectin was found to be stable after three free-thaw cycles, and with storage at − 20 and − 80°C for 12 weeks. The method is suitable for pharmacokinetic studies of moxidectin after oral administration to humans.
Pharmacokinetics assessment of moxidectin long-acting formulation in cattle
Veterinary Parasitology, 2007
The plasma kinetics disposition of moxidectin following a subcutaneous administration with a long-acting formulation (Cydectin 1 10%, Fort Dodge Animal Health, France) at the recommended dose of 1 mg kg À1 body weight was evaluated in Charolais cattle breed (five females weighing 425-450 kg) for 120 days. Furthermore, its concentration was measured in hair for the same period. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Moxidectin was first detected at 1 h after treatment for plasma (2.00 AE 1.52 ng ml À1 ) and at 2 days for hair (446.44 AE 193.26 ng g À1 ). The peak plasma concentration (C max ) was 55.71 AE 15.59 ng ml À1 and 444.44 AE 190.45 ng g À1 for plasma and hair, respectively. The mean calculated time of peak occurrence (T max ) was 3.40 AE 3.36 and 2 days for plasma and hair, respectively. The mean residence time (MRT) was 28.93 AE 2.87 and 13.32 AE 2.48 days for plasma and hair cattle. The area under concentration-time curve (AUC) was 1278.95 AE 228.92 ng day ml À1 and 2663.82 AE 1096.62 ng day g À1 for plasma and hair, respectively. At the last sampling time (120 days), the concentration was 1.91 AE 0.26 ng ml À1 and 0.69 AE 0.52 ng g À1 for plasma and hair, respectively. The bioavailability of this long-acting formulation of moxidectin is similar to that registered after subcutaneous administration of moxidectin in cattle at 0.2 mg kg À1 body weight. For the first time the moxidectin pharmacokinetics parameters in hair after a subcutaneous administration was described. The moxidectin profile concentrations in hair reflected that registered in plasma. The previous studies of efficacy have to be correlated to the extended period of absorption and distribution by the LA formulation due to the fivefold higher dose rate in comparison with the 1% injectable formulation (0.2 mg kg À1 body weight). #
Breed Differences on the Plasma Availability of Moxidectin Administered Pour-on to Calves
The Veterinary Journal, 2002
The pharmacokinetic profile of avermectin and milbemycin compounds is affected by different drug- and host-related factors. This work reports the influence of cattle breeds on the plasma kinetics of moxidectin (MXD) after topical (pour-on) administration. Parasite-free Aberdeen Angus and Holstein calves were treated with a commercial MXD pour-on formulation at 500 microg/kg. Blood samples were collected over a period of 35 days post-treatment and the recovered plasma was analysed by high performance liquid chromatography using fluorescence detection. MXD was detected in plasma from two hours up to 35 days post-treatment in animals from both breeds. A slow MXD absorption and delayed peak plasma concentration were observed in Aberdeen Angus compared to Holstein calves. Significant lower systemic availability (expressed as AUC) (P<0.01) and peak plasma concentration (C(max)) (P<0.05) were also observed in Aberdeen Angus calves, although the plasma mean residence time (MRT) and elimination half-lives (T(1/2el)) of MXD in both breeds were similar. The pharmacokinetic differences observed between cattle breeds contribute to explain the variability in the pattern of clinical efficacy for pour-on administered endectocide compounds reported in different field trials.
Journal of Dairy Research, 2004
Ivermectin (IVM) and moxidectin (MXD) are broad-spectrum endectocides belonging to the avermectin/milbemycin class of antiparasitic drugs not approved for use in dairy sheep. However, these compounds are widely used extra-label to control endo- and ecto-parasites in lactating dairy sheep. Effects of the route of administration on the pattern of IVM and MXD excretion in milk were comparatively characterized in lactating dairy sheep. The relationship between the milk and plasma disposition kinetics after subcutaneous (s.c.) and oral administration at 200 μg/kg body weight was also evaluated. IVM and MXD concentration profiles were measured in milk and plasma using a specific HPLC-based methodology. IVM and MXD were extensively distributed from the bloodstream to the mammary gland and large quantities, particularly for MXD, were excreted in milk. Residual concentrations of IVM were recovered in milk up to 11 d (oral treatment) or 25 d (s.c. treatment) post treatment. However, high MXD ...
In vitro Metabolism of 14C-Moxidectin by Hepatic Microsomes from Various Species
Veterinary Research Communications, 2001
Moxidectin is an antiparasitic drug widely used in cattle, sheep and companion animals. No data were available on its metabolism in wild species or in monogastrics. The in vitro metabolism of 14C-moxidectin was studied using hepatic microsomes from several different species: cow (Bos taurus), sheep (Ovis ovis), goat (Capra hircus), deer (Cervus dama), rat (Rattus norvegicus), pig (Sus scrofa and rabbit (Oryctolagus cuniculus). After separation and quantification by HPLC, the extent of metabolism of 14C-moxidectin was greatest with microsomes from sheep (32.7%) as compared to those from cows (20.6%), deer (15.4%), goats (12.7%), rabbits (7.0%) or rats (3.0%). The least metabolism occurred with microsomes from pigs, with 0.8% of total detected metabolites. A C29 monohydroxymethyl metabolite was detected in the greatest amounts, providing 0.4% out of the total detected radioactivity in pigs and 19.3% in sheep. In addition, the importance of P450 3A in the metabolism of 14C-moxidectin was confirmed by using in vivo induced P450 in combination with various P450 inhibitors.