Determination of oxpentifylline and three metabolites in plasma by automated capillary gas chromatography using nitrogen-selective detection

Burrows, Jennifer

doi:10.1016/0378-4347(87)80336-5

Cited by 17 publications

(5 citation statements)

References 7 publications

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“…Measurement of serum levels of pentoxifylline and its metabolites by capillary gas chromatography. The method used in the assay of plasma pentoxifylline and metabolites I, IV, and V was described by Burrows (2). The procedure included a single extraction of all species from plasma into chloroform, derivative formation (the trifluoracetyl derivative in the case of metabolite I and the methyl ester derivatives in the case of metabolites IV and V and their internal standard), and analysis by capillary gas chromatography.…”

Section: Albicansmentioning

confidence: 99%

Pharmacokinetics of Pentoxifylline and Its Metabolites in Healthy Mice and in Mice Infected with Candida albicans

Miller

Louie

Baltch

et al. 1998

Antimicrob Agents Chemother

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Pentoxifylline has immunomodulatory properties and has been shown to decrease organ damage and improve survival in animals with gram-negative sepsis or endotoxemia. This effect is mediated by a reduction in endotoxin-induced production of tumor necrosis factor alpha (TNF-α) by the host. In earlier studies, we observed an unexpected increase in mortality in mice infected with Candida albicans that were given pentoxifylline even though concentrations of TNF-α in serum were not affected. The current study was designed to determine whether the pharmacokinetics of pentoxifylline and its metabolites were altered in C. albicans-infected mice and, if so, whether these changes could have contributed to the increased mortality. Noninfected mice and mice infected with C. albicans were treated with pentoxifylline (60 mg/kg of body weight) intraperitoneally every 8 h. Serum was collected from animals after one (day 0), four (day 1), or seven (day 2) injections of pentoxifylline or saline (controls). The first dose was administered 6 h after C. albicans infection. Serum was pooled. Concentrations of pentoxifylline and metabolites I, IV, and V were determined by capillary gas chromatography. Renal function and hepatic profiles were assessed. Pharmacokinetic parameters (maximum concentration of pentoxifylline in serum, half-life, and area under the concentration-time curve from 0 h to infinity [AUC0–∞]) for all noninfected mice were similar and did not differ from those for day 0-infected mice. For day 1-infected mice, values of these three pharmacokinetic parameters for pentoxifylline and metabolite I were increased two- to fourfold over values for noninfected and day 0-infected mice. For metabolites IV and V, the AUC0–∞was increased approximately eightfold over control values. In addition, day 1-infected mice demonstrated evidence of renal and hepatic dysfunction. In summary, C. albicans infection produced marked changes in the pharmacokinetics of pentoxifylline and its metabolites in the mice. The high concentrations of pentoxifylline and its metabolites in serum attained in infected mice may have contributed to the increased mortality of mice with systemic candidiasis.

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Section: Albicansmentioning

confidence: 99%

Pharmacokinetics of Pentoxifylline and Its Metabolites in Healthy Mice and in Mice Infected with Candida albicans

Miller

Louie

Baltch

et al. 1998

Antimicrob Agents Chemother

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“…A single 400 mg dose of pentoxifylline given to human adults produced average peak plasma concentrations of 1.6 and 2.0 mg/L, respectively, for pentoxifylline and lisofylline, whereas respective elimination half-lives averaged 0.8 and 1.0 h (Smith et al, 1986). Analytical methods using gas chromatography and high-performance liquid chromatography with ultraviolet detection (HPLC-UV) have been developed for the detection of pentoxifylline and its metabolites (Burrows, 1987;Grasela and Rocci, 1987;Mancinelli et al, 1992). In general, however, methods based on these techniques have been limited by poor chromatographic resolution and low sensitivity, requiring complex sample concentration techniques or derivitization of the compounds of interest.…”

Section: Introductionmentioning

confidence: 99%

Use of liquid chromatography-tandem mass spectrometry for the analysis of pentoxifylline and lisofylline in plasma

Kyle

Adcock

Krämer

et al. 2005

Biomed. Chromatogr.

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A method was developed for the quantitation of pentoxifylline [1-(5-oxohexyl)-3,7-dimethylxanthine] and a primary active metabolite, lisofylline [1-(5-hydroxyhexyl)-3,7-dimethylxanthine], using high-performance liquid chromatography (HPLC)-tandem mass spectrometry. This method was developed in order to overcome problems encountered with HPLC-ultraviolet detection. The operating parameters of the electrospray interface (PE SCIEX, TurboIon Spray) and lens voltages of the triple-quadrupole detector (PE SCIEX 365) were optimized in positive ion mode to obtain the best sensitivity of the analytes. Collision-induced dissociation was used to produce fragment ions, and multiple reaction monitoring was used to quantitate pentoxifylline (m/z 279/181) and lisofylline (m/z 263/181). Dichloromethane was used to extract the drug, metabolite, and the internal standard (3-isobutyl-1-methylxanthine) from plasma. A reverse-phase C8(2) 150 x 1.0 mm HPLC column was used to resolve all three compounds in less than 6 min. Calibration curves were generated using peak area and were linear from 1 to 1000 ng/mL (R(2) > 0.99). The small sample volume, ease of extraction, and sensitivity provide advantages over more conventional methods of quantitation.

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“…PTX and active related metabolites have been assayed in biological fl uids by gas chromatography (GC) with selective nitrogen detection (NPD) through derivatization to trifl uoroacetyl products (Burrows and Jolley, 1985;Burrows, 1987;Smith et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC‐MS/MS

Sora¹,

Cristea²,

Albu³

et al. 2009

Biomedical Chromatography

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Analytical aspects related to the assay of pentoxifylline (PTX), lisofylline (M1) and carboxypropyl dimethylxanthine (M5) metabolites are discussed through comparison of two alternative analytical methods based on liquid chromatography separation and atmospheric pressure electrospray ionization tandem mass spectrometry detection. One method is based on a 'pure' reversed-phase liquid chromatography mechanism, while the second one uses the additional polar interactions with embedded amide spacers linking octadecyl moieties to the silicagel surface (C-18 Aqua stationary phase). In both cases, elution is isocratic. Both methods are equally selective and allows separation of unknowns (four species associated to PTX, two species associated to M1) detected through specific mass transitions of the parent compounds and owning respective structural confirmation. Plasma concentration-time patterns of these compounds follow typical metabolic profiles. It has been advanced that in-vivo formation of conjugates of PTX and M1 is possible, such compounds being cleaved back to the parent ones within the ion source. The first method was associated with a sample preparation procedure based on plasma protein precipitation by strong organic acid addition. The second method used protein precipitation by addition of a water miscible organic solvent. Both analytical methods were fully validated and used to assess bioequivalence between a prolonged release generic formulation and the reference product, under multidose and single dose approaches.

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Determination of oxpentifylline and three metabolites in plasma by automated capillary gas chromatography using nitrogen-selective detection

Cited by 17 publications

References 7 publications

Pharmacokinetics of Pentoxifylline and Its Metabolites in Healthy Mice and in Mice Infected with Candida albicans

Pharmacokinetics of Pentoxifylline and Its Metabolites in Healthy Mice and in Mice Infected with Candida albicans

Use of liquid chromatography-tandem mass spectrometry for the analysis of pentoxifylline and lisofylline in plasma

Bioanalysis of pentoxifylline and related metabolites in plasma samples through LC‐MS/MS

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