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A second-generation chlorin-based photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) has shown tremendous therapeutic potential in clinical trials in the treatment of esophageal cancer. Herein, we have developed and validated a bioanalytical method for estimation of HPPH in rat plasma using High Performance Liquid Chromatography (HPLC) with a photo diode array (PDA) detector. The method was applied for carrying out pharmacokinetic study of HPPH. Further pharmacokinetic modeling was carried out to understand the compartment kinetics of HPPH. The developed method was fully validated as per the United States Food and Drug Administration (US-FDA) guidelines for bioanalytical method validation. The linearity of the method was in the range of 250–8000 ng/mL, and the plasma recovery was found to be 70%. Pharmacokinetic parameters were evaluated and compared via non-compartment analysis and compartment modeling after the intravenous (i.v.) bolus administration in rats using Phoenix WinNonlin 8.0 (Certara™, U.S.A.). From the obtained results, we hypothesize that the HPPH complies with two compartmental pharmacokinetic model. Furthermore, it was observed that HPPH has the rapid distribution from the central compartment to peripheral compartment along with slow elimination from peripheral compartment.

A simple, sensitive and robust HPLC–PDA assay was developed and validated for rapid determination of donepezil hydrochloride (DNP), a potent acetylcholinesterase inhibitor in rat plasma and tissues. All biological samples were prepared by the solid-phase extraction method using loratadine as an internal standard. Separation of the analytes was achieved on a Waters Nova-Pak C18 column (3.9 × 150 mm, 4 μm) using an isocratic mobile phase of acetonitrile and ammonium formate (pH 6.4; 0.01 M) (62 : 38% v/v) at a flow rate of 1 mL min−1. All validation parameter results were within the acceptable range described in the guidelines for bioanalytical method validation. The method showed linearity in the concentration range of 50–5000 ng mL−1 with LOD of 20 ng mL−1 and LLOQ of 50 ng mL−1. Moreover, the advantage of this method over previously published methods is the short analysis run time of 6 min in HPLC itself, alongside its application not only for plasma samples but also in tissues, with low LLOQ. The method was successfully applied for studying the compartmental pharmacokinetics, tissue distribution and pharmacodynamics. A two-compartmental micro model was statistically fitted for the assessment of pharmacokinetic parameters. The tissue distribution studies suggest that the kidneys, lungs and liver are the primarily responsible organs for metabolism and elimination of DNP. Pharmacodynamic studies were performed by measuring acetylcholinesterase inhibitory activity of DNP, which indicated that the pharmacokinetic and pharmacodynamic data are in correlation with each other.

The difference in tissue distribution of Ketorolac and its enantiomers were investigated in wistar rats. Separate high performance liquid chromatographic method was developed and validated for determination of Ketorolac and its enantiomers. Oyster BDS (150×4.6 mm id., 5 μm particle size) column was used for determination of concentration of Ketorolac. Ketorolac enantiomers were determined using Chiral-AGP column (100×4.0 mm I.D., particle size 5 μ, Chrom tech Ltd, Sweden). Detection was done at wavelength of 322 nm using an ultraviolet detector in the analytical system. Ketorolac enantiomers exhibit difference in their disposition in Wistar rats. In kidney, there was a significant difference in pharmacokinetic parameters. The C max was nearly 4 times and AUC 0–∞ was found to be more than double for S (−) Ketorolac than that of R (+) Ketorolac. MRT, K e and t 1/2 differ significantly in kidney. In liver, C max was found to be approximately 69% higher for S (−) Ketorolac compared to R (+) Ketorolac. AUC 0–∞ did not differ significantly for the enantiomers in liver. In liver, S (−) Ketorolac eliminated very fast in comparison to R (+) Ketorolac having t 1/2 (one third) in comparison to R (+) Ketorolac. In lungs, there was no difference observed for C max and other parameters but AUC 0–∞ was found to be marginally higher for S (−) ketorolac.