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

Kyle, Patrick B.; Adcock, Kim G.; Krämer, Robert; Baker, Rodney C.

doi:10.1002/bmc.441

Cited by 13 publications

(10 citation statements)

References 17 publications

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“…On our knowledge, a single approach has been reported for assaying PTX and M1 in plasma by means of liquid chromatography-atmospheric pressure electrospray ionization-tandem mass spectrometry detection [LC-(ESI)MS/MS] (Kyle et al, 2005). Reported LOQ value found for PTX falls in the 1 ng/mL level.…”

Section: Introductionmentioning

confidence: 98%

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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Section: Introductionmentioning

confidence: 98%

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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“…Another important parameter is temperature, because separation at increased temperature reduces the analysis time and also decreases the column backpressure owing to the decreased viscosity at higher temperature [ 65 ]. In addition to C18 silica columns as the gold standard in RP-HPLC, other packing materials may be used as well, shorter alkyls C12 [ 54 , 66 ] and C8 [ 67 – 69 ], a medium-polarity nitrile column [ 70 ] for polar analytes or longer alkyls such as C30 for hydrophobic drugs [ 34 ]. Hydrophilic interaction chromatography (HILIC) is based on the hydrophilic interactions between ionic analytes and zwitterionic groups covalently bonded to silica or polymer beads, e.g., –CH 2 N + (CH 3 ) 2 CH 2 CH 2 CH 2 SO 3 - , which provides a separation mechanism orthogonal to that of RP-HPLC [ 71 ].…”

Section: Introductionmentioning

confidence: 99%

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

2008

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Applications of tandem mass spectrometry (MS/ MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002)(2003)(2004)(2005)(2006)(2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H] + and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H] -ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MS n analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well.

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“…There were few LC-MS methods proposed for quantification of PTF alone or along with its metabolites. [20][21][22][23][24] Kyle's liquid chromatographytandem mass spectrometry (LC-MS/MS) method 22 has employed 0.5 ml human plasma, processed by liquid-liquid extraction (LLE) technique using less environment friendly solvent dichloromethane with the run time of more than 5 min. This method also has not been applied for pharmacokinetic study.…”

Section: Pentoxifyllinementioning

confidence: 99%

Development and validation of bioanalytical liquid chromatography–tandem mass spectrometry method for the estimation of pentoxifylline in human plasma: Application for a comparative pharmacokinetic study

Dodda

Ajitha

Polagani³

et al. 2018

Eur J Mass Spectrom (Chichester)

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A method for bioanalysis of pentoxifylline in human plasma was developed using liquid chromatography–tandem mass spectrometry, which is simple, specific, and sensitive. Pentoxifylline D5 was used as the internal standard. Employing only 100 µl of human plasma, processing was done with solid-phase extraction technique. The analyte and the internal standard were separated from endogenous components on Ace phenyl column using a mixture of 5 mM ammonium acetate buffer and high performance liquid chromatography grade acetonitrile (60:40, v/v) as mobile phase at a flow rate of 1 ml/min. The linearity of the method was in the range of 3–1200 ng/ml with r2 > 0.99. Positive ion MRM mode was used for the detection of the analyte and the internal standard. The method was validated as per the US Food and Drug Administration guidelines and the results were within the acceptance limits. The proposed method was applied for comparative pharmacokinetic study of pentoxifylline after oral administration of 400 and 600 mg tablets to South Indian male subjects under fed conditions.

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

Cited by 13 publications

References 17 publications

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

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

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Development and validation of bioanalytical liquid chromatography–tandem mass spectrometry method for the estimation of pentoxifylline in human plasma: Application for a comparative pharmacokinetic study

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