• Title, Summary, Keyword: Beagle dog

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Development and Validation of a Robust LC-MS/MS Method for the Simultaneous Quantification of Doxifluridine and its Two Metabolites in Beagle Dog Plasma

  • Baek, In-Hwan;Chae, Jung-Woo;Chae, Han-Jung;Kwon, Kwang-Il
    • Bulletin of the Korean Chemical Society
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    • v.31 no.8
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    • pp.2235-2241
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    • 2010
  • A reverse-phase HPLC method with detection by mass spectrometry is described for the simultaneous determination of doxifluridine and its two active metabolites, 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUrd), in beagle dog plasma. The optimal chromatographic separation was achieved on a Waters $Xterra^{(R)}$ $C_{18}$ column ($4.6{\times}250\;mm$ i.d., $5\;{\mu}m$ particle size) with a mobile phase of 0.1% formic acid in a mixture of 99% methanol and purified water (99:1, v/v). The developed method was validated in beagle dog plasma with a lowest limit of quantification of $0.05\;{\mu}g/mL$ for both doxifluridine and 5-FU, and $0.2\;{\mu}g/mL$ for 5-FUrd. Doxifluridine and its two metabolites were stable under the analysis conditions, and intra- and inter-day accuracies exceeded 92.87%, with a precision variability ${\leq}11.34%$ for each analyte. Additionally, the method for quantifying doxifluridine and its two metabolites, 5-FU and 5-FUrd, in beagle dog plasma was applied successfully to the analysis of pharmacokinetic samples.

Liquid Chromatography-Tandem Mass Spectrometry Analysis of Riboflavin in Beagle Dog Plasma for Pharmacokinetic Studies

  • Jeong, Hyeon Myeong;Shin, Beom Soo;Shin, Soyoung
    • Mass Spectrometry Letters
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    • v.11 no.1
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    • pp.10-14
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    • 2020
  • Riboflavin is a water-soluble vitamin, which serves as a precursor to flavin mononucleotide and flavin adenine dinucleotide. This study aimed to develop a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for the quantification of riboflavin in the Beagle dog plasma. This method utilized simple protein precipitation with acetonitrile and 13C4, 15N2-riboflavin was used as an internal standard (IS). For chromatographic separation, a hydrophilic interaction liquid chromatography (HILIC) column was used with gradient elution. The mobile phase consisted of 0.1% (v/v) aqueous formic acid with 10 mM ammonium formate and acetonitrile with 0.1% (v/v) formic acid. Since riboflavin is an endogenous compound, 4% bovine serum albumin in phosphate buffered saline was used as a surrogate matrix to prepare the calibration curve. The quantification limit for riboflavin in the Beagle dog plasma was 5 ng/mL. The method was fully validated for its specificity, sensitivity, accuracy and precision, recovery, and stability according to the US FDA guidance. The developed LC-MS/MS method may be useful for the in vivo pharmacokinetic studies of riboflavin.

Four-Week Intravenous Toxicity of DA-3030 (G-CSF) in Beagle Dogs (Beagle dog에서 DA-3030(G-CSF)의 정맥내 4주간 반복투여 독성)

  • 이영순;조재진;남기환;서광원;강성근;박재학;김원배
    • Biomolecules & Therapeutics
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    • v.2 no.3
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    • pp.260-269
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    • 1994
  • This study was performed to determine the toxic effect of DA-3030(granulocyte-colony stimulating factor, G-CSF) in beagle dogs. DA-3030(G-CSF) was injected intravenously at doses of 115 $\mu\textrm{g}$/kg/day, 11.5 $\mu\textrm{g}$/kg/day and 1.15 $\mu\textrm{g}$/kg/day seven days per week for 28 days. After completion of the treatments, the dog were necropsied. The number of dead animal was zero in all groups. No specific clinical sign was found, either. In hematological results, WBC was significantly increased dose-dependently in treated groups. In histopathological findings, megakaryocyte and rubricyte were found in the liver and spleen at the dose of 115 $\mu\textrm{g}$/kg/day. Therefore, we could find the extramedullary hematopoiesis was increased. Megaka yocyte and rubricyte were increased in bone marrow, too. In conclusion, those signs were estimated the pharmacological effect of DA-3030(G-CSF). According to the results, non toxic dose of DA-3030(G-CSF) was higher than 115 $\mu\textrm{g}$/kg/day.

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Beagle dogs parentage testing by using 22 ISAG microsatellite markers

  • Ji, Hye-jung;Kim, Eun-hee;Lee, Kyoung-kap;Kang, Tae-young;Lee, Joo-myoung;Shin, Hyoung-doo;Kim, Lyoung-hyo;Yun, Young-min
    • Korean Journal of Veterinary Research
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    • v.47 no.4
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    • pp.457-460
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    • 2007
  • The objective of the study was to establish routine parentage testing system in Beagle dogs using 22 ISAG (International Society for Animal Genetics) canine microsatellite markers (2005). Blood collections were obtained from a mother dog, 4 candidate father dogs and 3 offspring (n = 8). Genomic DNA samples were extracted from 8 Beagle dogs blood for PCR analysis. PCR products for the allele were analyzed by ABI 3130 DNA Sequencer and GeneScan (Ver 3.0) analysis and Genotyper (Ver. 2.1) software. The genetic relationship of mother and 3 offspring as well as one father dog among 4 candidate father dogs was confirmed by microsatellite allele analysis. The results of locus for amelogenin, which was designed for sexing, were matching with real gender among 8 Beagle dogs (female; 217/217 homozygosity, male; 179/217 heterozygosity). Twenty two ISAG microsatellite markers are useful the parentage test of Beagle dogs. In addition, amelogenin is an applicable marker to detecting real sex in dogs.

Establishment Percutaneous Administration Method in Beagle Dog

  • Han, Su-Cheol;Bae, Ju-Hyun;Cha, Shin-Woo;Jiang, Cheng-Zhe;Tarumoto Y.;Kim, Choong-Yong;Chung, Moon-Koo
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.154-154
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    • 2003
  • The primary routes of drug administration include oral, intramuscular, subcutaneous and intravenous dosing for toxicological risk assessment purpose in dog. There has been an increase applying transdermal patches as an alternate method for systemic delivery. The present study was performed to establish the transdermal delivery method of medicated ointment, liquid and powder material to beagle dog.(omitted)

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Metastatic thyroid C-cell carcinoma in a beagle dog

  • Lee, So-Ra;Lee, Mi-Kyoung;Youp, Kyoung-A;Lee, Ah-Ra;Won, Sung-Jun;Kim, Myung-Chul;Kim, So-Yeon;Kim, Yongbaek
    • Korean Journal of Veterinary Research
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    • v.53 no.3
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    • pp.189-192
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    • 2013
  • An adult beagle dog was presented with a cervical mass detected by palpation and computed tomography. Fine needle aspirates revealed numerous epithelial cells with plasmacytoid appearance and frequent naked nuclei. Histologically, the mass consists of multiple packets of neoplastic cells and extensive areas of necrosis and fibrosis. Neoplastic cells were also found in submandibular lymph nodes. Immunohistochemistry showed that neoplastic cells were positive for calcitonin and negative for thyroglobulin. Based on these findings, the cervical mass was diagnosed as thyroid C-cell carcinoma. Almost one year after the surgical excision, the dog remains healthy without any symptom of recurrence or metastasis.

Simultaneous Determination of Doxifluridine and 5-FU in Liver and Intestine Tissue Using LC/MS/MS (LC/MS/MS를 이용한 원숭이 및 비글견의 간 및 장관 조직에서의 Doxifluridine과 대사체 5-FU 동시분석법 개발)

  • Woo, Young-Ah;Kim, Ghee-Hwan;Jeong, Eun-Ju;Kim, Choong-Yong
    • YAKHAK HOEJI
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    • v.52 no.2
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    • pp.93-100
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    • 2008
  • A liquid chromatographic method with tandom spectrometric detection (LC/MS/MS) for the simultaneous determination of doxifluridine and its active metabolite, 5-fluorouracil (5-FU) was developed over the concentration range of $5{\sim}2000$ ng/ml, respectively. Doxifluridine, 5-FU and internal standard, 5-chlorouracil (5-CU), were extracted from liver and intestine tissue via protein precipitation. Acetonitrile was used as the extraction solvent and the supernatant was evaporated and reconstructed in mobile phase. Optimum chromatographic separation was achieved on a Agilent Zorbax $C_{18}$ ($100\;mm{\times}2.1\;mm$, $3.5\;{\mu}m$) column with mobile phase run in isocratic with methanol : water (20 : 80, v/v). The flow rate was 0.2 ml/min with total cycle time of 5 min. The lower limit of quantification was validated at 5.0 ng/ml of liver and intestine tissue, for both doxifluridine and 5-FU, respectively. The intra-day and inter-day precision and accuracy of quality control (QC) samples were <11% coefficient of variation and <7% relative error from theoretical concentration for both analytes. In addition, the special designed stability study was performed, because the metabolism of doxifluridine occurs spontaneously even in ice bath for monkey liver. The stability of doxifluridine in liver and intestine of monkey and beagle dog was compared. It was found that bioanalytical validation could not be performed for the monkey liver; however, beagle dog's liver has relatively low speed of metabolism compared to monkey liver and instead of monkey liver, beagle dog's liver could be used for the validation. Bioanalytical validation could be performed in monkey intestine. Eventually, this developed method for liver and intestine will be useful in support of the toxicokinetic and pharmacokinetic studies of doxifluridine and 5-FU.

Acute Toxicity of CJ-50001 (rG-CSF) in Rats and Dogs (CJ-50001 (rG-CSF)의 Rat 및 Dog에서의 급성독성)

  • 임동문;조효진;김달현;이현수;고형곤;김제학;김현수
    • Toxicological Research
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    • v.13 no.3
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    • pp.293-296
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    • 1997
  • The acute toxicity study of CJ-50001, a recombinant granulocyte-colony stimulating factor (rG-CSF), was performed in Sprague Dawley (SD) rats and beagle dogs. CJ-50001 was administered up to maximum dose 5,000 $\mu\textrm{g}$/kg (i.v.) and 10,000 $\mu\textrm{g}$/kg (p.o.) in SD rats and 5,000 $\mu\textrm{g}$/kg (i.v.) in beagle dogs. In these experiments, there were no death and harmful clinical changes which were related to CJ-50001. In conclusion, $LD_{50}$ of CJ-50001 is over 5,000 $\mu\textrm{g}$/kg, i.v. in SD rats and beagle dogs, and over 10,000 $\mu\textrm{g}$/kg, p.o. in SD rats.

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Follicular Cysts of a Beagle Dog in Diestrous Stage (비글개에서 발정 휴지기중의 난포낭종)

  • Kim, H.S.;Kang, H.G.;Kim, I.H.;Lee, C.S.;Lee, K.C.;Lee, D.Y.;Mun, J.S.
    • Journal of Embryo Transfer
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    • v.22 no.1
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    • pp.33-37
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    • 2007
  • A 2 years old female beagle dog was examined because of the vaginal discharge and vaginal swelling at 7th day after mating. Abdominal ultrasonography revealed multiple follicular cysts on both ovaries. Also, the ratio of superficial cells was above 90% based on vaginal cytology. She was still in standing heat, with the tail deflected up and flagging when a male sniffed the vulva and attempted to mount. The dog was diagnosed with multiple follicular cysts by vaginal cytology, clinical signs and ultrasonography. The dog was treated with GnRH $50{\mu}g$ injection by intramuscularly. The sizes of the cysts were decreased two weeks after GnRH treatment, and then the dog delivered an offspring at 68th day after last mating. To confirm the stage of estrous cycle, we performed hormone analyses, retrospectively $Estradiol-17{\beta}$ concentration was 78pg/ml at diagnosis. Progesterone concentration was 6.9ng/ml at the last mating, and 66.9ng/ml at diagnosis. Therefore, we confirmed that follicular cysts was observed during diestrous stage in a beagle dog.

Guided Bone Regeneration with a PDGF-BB-Ioaded Resorbable Membrane in the Dehisced Implant of the Beagle Dog (치아매식술에 이용한 혈소판 유래 성장인자 함유 흡수성 차폐막의 골유도 재생효과)

  • Kwon, Young-Hyuk;Park, Joon-Bong;Herr, Yeek;Chung, Chong-Pyung;Han, Soo-Bog;Lee, Seung-Jin
    • Journal of Periodontal and Implant Science
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    • v.28 no.3
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    • pp.431-451
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    • 1998
  • 4 beagle dogs aged over one and half years and weighed 15 to 16 Kg were utilized in this study. Experimental dehiscent defects were made in the mandibular edentulous area after removal of lower premolar. e-PTFE membrane resorbable membrane, and PDGF-BB-loaded resorbable membrane were covered at the dehiscent defects around the dental implants respectively. Animal was sacrificed at 1, 2, 3 months respectively. Non-decalicifed specimens were made and mutiple-stained for light microscopic study. The results were as follows: 1. Dehiscent defects around the implant installed in the beagle dog were an excellent defect model for studying guided bone regeneration. 2. Fibroblasts penetrated into expanded-PTFE membrane was observed and inflammatory cell infiltration was also observed around the membrane. 3. Resorbable membrane was degradaded and resorbed at 1 month after application to the dehiscent defect. Though multinucleated giant cells were observed adjacent to the membrane, that had no reverse effect on the boe regeneration. 4. PDGF-BB-Ioaded resorbable membrane was same capability as the resorbable membrane and e-PTFE membrane in the guided bone regeneration. 5. PDGF-BB-Ioaded resorbable membrane-applied site was better than resorbable membrane-applied site in the speed and maturity of bone formation. Within the above results, it was suggested that PDGF-BB-Ioaded resorbable membrane might have same bone regeneration capacity as nonresorbable membrane in the dehisced implant of the beagle dog and potentiality to use in human subjects.

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