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生物分析および生物医学ジャーナル

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音量 3, 問題 6 (2011)

研究論文

Effects of Concurrent Administration of Meloxicam on Pharmacokinetic Parameters of Enrofloxacin in Turkeys

Reetu Toppo, B.K.Roy and Anil K.Mishra

The pharmacokinetic studies of enrofloxacin was conducted in eighteen turkeys (1 to 1.5 years age) weighing between 3 to 4 kg following single i.v. dose (10 mg/kg b.w.) alone and with meloxicam (1 mg/kg b.w.). Quantitative estimation of enrofloxacin and meloxicam was done by high performance liquid chromatography. The maximum concentration of drug in plasma (Cpmax) of enrofloxacin with meloxicam (8.42 ± 0.40 μg/ml) was not significantly different from that of enrofloxacin alone (9.68 ± 0.44 μg/ml). Pharmacokinetic parameters of enrofloxacin alone (C°p =10.38±0.43 μg/ml, t½β =2.73±0.12 h, MRT = 3.65±0.21 h, ClB =8.41±0.66 ml/kg/min, Vdarea =1.95±0.08 L/kg) as compared to when it was administered with meloxicam ( C°p =9.35±0.62 μg/ml, t½β =2.70±0.13 h, MRT =3.73±0.18 h, ClB =9.79±0.84 ml/kg/min, Vdarea =2.26±0.15 L/kg) in turkeys did not differ significantly.

The t½β of meloxicam with enrofloxacin (2.50±0.08 h) was significantly shorter as compared to meloxicam alone (3.03±0.18 h). Based on pharmacokinetic studies ENR may be injected at dose rate of 4.5 mg/kg i.v. at an interval of 20.38 h in turkeys.

研究論文

Quantification of Fentanyl in Human Serum by Column-Switching Liquid Chromatography and Tandem Mass Spectrometry

Torben Breindahl, Kristian Kjær Petersen, Mark Lillelund Rousing, Kirsten Andreasen, Lars Arendt-Nielsen and Peter Hindersson

Analytical methods for pharmacokinetic studies with quantification of the highly potent anaesthetic drug fentanyl in serum must be rugged, sensitive, precise and accurate. To address these analytical demands and facilitate an automated approach to sample clean-up, a new method was developed for human serum using back-flush columnswitching and high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS). Prior to injection, protein precipitation in trichloroacetic acid was performed in each sample. Samples were diluted with internal standard (D5-fentanyl) in 10% (w/v) trichloroacetic acid, kept at 4oC for 20 min and centrifuged followed by injection of 40μL supernatant onto a BioTrap 500 MS extraction column. Using a time programmed six-port valve switch, the extracted drug was back-flushed onto a Zorbax SB-Aq analytical column, gradient eluted and finally detected after electrospray ionisation with multiple reaction monitoring (MRM) of the transitions m/z 337 → m/z 188 and m/z 342 → m/z 188 for fentanyl and D5-fentanyl, respectively. Mean inter-assay accuracy (n=5) ranged from 93 to 101 % and inter-assay precision (n=5) ranged from 3.7 to 9.4% (C.V.). The method was used in a preliminary study of 4 patients after application of transdermal patches and found fully applicable for future pharmacokinetic studies. This is the first on-line, column-switching LC-MS/MS method validated and demonstrated suitable for quantification of fentanyl in human serum.

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