LC–MS/MS method for the simultaneous determination of clarithromycin, rifampicin and their main metabolites in horse plasma, epithelial lining fluid and broncho-alveolar cells

Oswald, Stefan; Peters, Jette; Venner, Monica; Siegmund, Werner

doi:10.1016/j.jpba.2011.01.019

Cited by 40 publications

(26 citation statements)

References 21 publications

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“…The assay for AZM in plasma, tissues, and ISF was performed by using a previously reported method, with minor modifications (18)(19)(20). Briefly, to determine AZM levels, 5 l of ISF was diluted with 95 l of distilled water.…”

Section: Methodsmentioning

confidence: 99%

Transport of Azithromycin into Extravascular Space in Rats

Kobuchi

Aoki

Inoue

et al. 2016

Antimicrob Agents Chemother

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f Recent clinical trials showed a prolonged retention of subinhibitory concentrations of unbound azithromycin in the interstitial fluid of soft tissues despite the fact that azithromycin is extensively distributed in tissues. In these clinical trials, interstitial fluid samples were obtained by using the microdialysis method, and it was established that drug concentrations represent proteinunbound drug concentrations. The present study was designed to measure total azithromycin concentrations in the interstitial fluid of the skin of rats by directly collecting interstitial fluid samples from a pore formed on the skin by a dissolving microneedle array. The total azithromycin concentrations in interstitial fluid of the skin were about 4 to 5 times higher than those in plasma throughout the experimental period, and stasis of the azithromycin concentration in interstitial fluid was observed when the concentration of azithromycin in plasma was at the lower limit of quantification. In addition, the skin/plasma concentration ratio transiently increased after dosing (from 4.3 to 83.1). Our results suggest that azithromycin was trapped inside white blood cells and/or phagocytic cells in not only blood but also interstitial fluid, resulting in a high total azithromycin concentration and the retention of its antimicrobial activity at the primary infection site. The stasis of azithromycin in interstitial fluid and skin would lead to long-lasting pharmacological effects (including those against skin infection) at concentrations exceeding the MIC.

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Section: Methodsmentioning

confidence: 99%

Transport of Azithromycin into Extravascular Space in Rats

Kobuchi

Aoki

Inoue

et al. 2016

Antimicrob Agents Chemother

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“…CLR and 14-hydroxyclarithromycin (14-OH-CLR) were quantified in plasma, lavage fluid, and BALC using a validated liquid chromatography-tandem mass spectrometry method as described recently (Oswald et al, 2011a). The limit of quantification for all matrices was 2.5 ng/ml.…”

Section: Methodsmentioning

confidence: 99%

Oral Absorption of Clarithromycin Is Nearly Abolished by Chronic Comedication of Rifampicin in Foals

Peters

Block²,

Oswald³

et al. 2011

Drug Metab Dispos

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ABSTRACT:The delivery of clarithromycin (CRL) to its site of action in bronchial/alveolar epithelial cells (EC), bronchial epithelial lining fluid (ELF), and bronchoalveolar lavage cells (BALC) may be influenced by CYP3A4 and the drug transporters, ATP-binding cassette (ABC) B1 and ABCC2 and organic anion-transporting polypeptides (OATPs), which can be modulated and/or up-regulated via the nuclear pregnane X receptor (PXR) by rifampicin (RIF). Therefore, we evaluated the disposition and pulmonary distribution of CLR (7.5 mg/kg b.i.d., 21 days) and expression of ABCB1, ABCC2, OATP1A2, and OATP2B1 in EC and BALC before and after comedication of RIF (10 mg/kg b.i.d., 11 days) in nine healthy foals (41-61 days, 115-159 kg) in which the genetic homology of drug transporters is close to that of their human analogs. After RIF comedication, relative bioavailability of CLR decreased by more than 90%. Concentrations in plasma (29.8 ؎ 26.3 versus 462 ؎ 368 ng/ml), ELF (0.69 ؎ 0.66 versus 9.49 ؎ 6.12 g/ml), and BALC (10.2 ؎ 10.2 g/ml 264 ؎ 375 g/ml; all P < 0.05) were lowered drastically, whereas levels of the metabolite 14-hydroxyclarithromycin were not elevated despite higher 4␤-hydroxycholesterol/cholesterol plasma concentration ratio, a surrogate for CYP3A4 induction. In the presence of CLR, ABCC2 and PXR mRNA contents were significantly and coordinately (r 2 ‫؍‬ 0.664, P < 0.001) reduced in BALC after RIF. In EC, mRNA expression of OATP1A2 increased but that of OATP2B1 decreased (both P < 0.05). RIF interrupts oral absorption and decreases CRL plasma levels below the minimal inhibitory concentration for eradication of Rhodococcus equi. Evidence that RIF influences the cellular uptake of CLR in bronchial cells and the PXR expression in BALC in the presence of high CLR concentrations exists.

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“…These methods are based either on the derivatization of the molecule before the chromatographic column due to its low absorptivity or on the ion-pair formation followed by electrochemical detection with amberometric or coulometric detection [9][10][11][12][13][14][15] . There also references using spectrochemical methods 16,17 , gas chromatography, microbiological methods, thin layer chromatography (TLC), mass spectrometry 18,19 , capillary electrophoresis 20 , HPLC 21,22 and electrophoresis 23 .…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an HPLC Method for the Determination of the macrolide antibiotic Clarithromycin using Evaporative Light Scattering Detector in raw materials and Pharmaceutical Formulations

Tzouganaki

Koupparis

2017

Mediterr.J.Chem.,

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In this work, ELS-Detector has been used for the development of an HPLC method for the determination of clarithromycin in pharmaceutical formulations (tablets and pediatric suspension). Isocratic reversed phase HPLC approach has been developed using a C-18 column (Waters Spherisorb 5 μm ODS2, 4.6x250 mm) and a mobile phase consisting of acetonitrile / aqueous trifluoroacetic acid as pairing reagent. Experimental parameters (temperature of heated drift tube, flow rate of mobile phase, gas flow rate, mobile phase composition) were optimized. Clarithromycin’ s stability was thoroughly examined in different solvent systems. Using the optimized conditions the working range was 5-100 μg/mL (upper limit can be increased considerably), with a detection limit of 4.5 μg/mL (6x10-6 M). The method was validated as per ICH guidelines. The retention time was 4.7 min. The method was successfully applied for the content assay of clarithromycin formulations.

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LC–MS/MS method for the simultaneous determination of clarithromycin, rifampicin and their main metabolites in horse plasma, epithelial lining fluid and broncho-alveolar cells

Cited by 40 publications

References 21 publications

Transport of Azithromycin into Extravascular Space in Rats

Transport of Azithromycin into Extravascular Space in Rats

Oral Absorption of Clarithromycin Is Nearly Abolished by Chronic Comedication of Rifampicin in Foals

Development and Validation of an HPLC Method for the Determination of the macrolide antibiotic Clarithromycin using Evaporative Light Scattering Detector in raw materials and Pharmaceutical Formulations

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