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.

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.

Development of a HPTLC method for in-process purity testing of pentoxifylline.

A HPTLC method for the separation and identification of pentoxifylline and related substances, impurities of reaction partners, and side reaction products has been developed using different mobile and stationary phases. For quantitative assay of possible by-products as impurities, LiChrospher RP-18 F254s chromatoplates, acetone-chloroform-toluene-dioxane (2:2:1:1 v/v) as a mobile phase, and detection at 275 nm were employed. Linearity (r > or = 0.997), recovery (86.5-115.5%), and determination limit (0.1-0.6%) were evaluated and found to be satisfactory. This method enables monitoring of the synthesis, as well as purity control of pentoxifylline-containing raw materials and pharmaceuticals.

Application of micellar electrokinetic chromatography to the quality control of pharmaceutical formulations: the analysis of xanthine derivatives.

Micellar electrokinetic chromatography (MEKC) has been applied to the analysis of three different drugs. Although belonging to different therapeutic classes, all these drugs contain xanthine derivatives as active substances. Pentoxifylline was separated from eight related xanthines. Quantitative MEKC was applied to determine impurities (caffeine and xanthine) in the purified drug at the 0.05-0.1% level and also for the determination of the active substance in Agapurin tablets. Ethofylline and theophylline were separated from ephedrine and mebrophenhydramine and determined in Xantedrylettae tablets while caffeine was separated from mephenhydramine and determined in Kinedryl tablets. In all cases, simple borate buffers with sodium dodecyl sulfate as the surfactant were satisfactory and little separation optimization was required. The relative standard deviation (RSD) of the migration times was better than 1% while the RSD of the observed areas was better than 2%. This demonstrates that MEKC is a valuable alternative for the traditional high-performance liquid chromatography analysis of drugs and drug formulations.