Pharmacokinetics.

A simple, rapid and sensitive liquid chromatography / electro spray ionization tandem mass spectrometry (LC–ESI–MS/MS) assay method has been proposed for the determination of apremilast in human plasma samples using apremilast d5 as internal standard (IS). Analyte and the IS were extracted from the 200 µL of human plasma via simple solid–phase extraction. The Chromatographic separation was obtained on a C18 column operating at a flow rate of 1.0 mL/min by using a mobile phase comprising of mixture of 5mm ammonium acetate in 0.2% formic acid buffer (15:85, v/v) and acetonitrile. A linear (r2 ³ 0.99) of the calibration curve was obtained over the concentration range of 2.03–808 ng/mL.  As per FDA guidelines method validation was performed and the results met the acceptance criteria. The intra–day and inter–day precision (%CV) and accuracy results in five validation batches across five concentration levels were well within the acceptance limits. To analyze the more number of samples in short time, thus increasing the productivity a short run time of 2.25 min for each sample was applied and this was made possible. The method was successfully applied to a pharmacokinetic study in humans.

In the present paper, the authors described a novel Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of montelukast in human plasma using montelukast d6 as internal standard (IS). After solid phase extraction (SPE), the analyte and the IS were chromatographed on a C18 columns using a isocratic mobile phase composed of acetonitrile–5mM ammonium acetate (80:20, v/v) pumped at a flow rate of 0.8mL/min. The proposed method was validated in the range of 5.01–599.91 ng/mL as per the US FDA guidelines. Precision and accuracy results were calculated using five successful calibration curves. Analyte stability in true samples and in plasma samples under different conditions were established and results met the acceptance criteria. The chromatographic run time was set at 3 min, which makes the proposed method is high through put. The method was successfully applied to a pharmacokinetic study in healthy South Indian male subjects under fasting condition.

  A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of two lipid lowering agents rosuvastatin and fenofibric acid in human plasma. Lovastatin was used as an internal standard. Analytes and the internal standard were extracted from human plasma by liquid-liquid extraction technique using a 50:50, v/v mixture of ethyl acetate and diethyl ether. The reconstituted samples were chromatographed on a C18 column by using a 80:20, v/v mixture of acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 1.0 mL/min. The calibration curve obtained was linear (r2 ³ 0.99) over the concentration range of 0.10-80.00 ng/mL for rosuvastatin and 50-9003 ng/mL for fenofibric acid. The multiple reaction monitoring mode was used for quantification of ion transitions at m/z 482/258, 319/233 and 405/199 for the rosuvastatin, fenofibric acid and the internal standard, respectively. The results of the intra-day and inter-day precision and accuracy study results were well within the acceptable limits. A run time of 3.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was successfully applied for the determination of the fenofibric acid in real time plasma samples for pharmacokinetic studies. Key words: Rosuvastatin, Fenofibric acid, human plasma, LC-MS/MS quantification, Pharmacokinetics.

  The aim of this study was to evaluate the bioequivalence of test and reference losartan potassium 50 mg formulations in healthy volunteers. This open label, balanced, single-dose, randomized, 2-period, crossover oral bioequivalence study was conducted in 54 healthy human adult subjects under fasting condition. Subjects received losartan 50 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 48 hours. The plasma concentrations of losartan and its active metabolite were determined by a validated method using LC/MS/MS. Pharmacokinetic parameters Cmax, Tmax, t1/2, AUC0-t, AUC 0-∞, and kel, were determined for both the  formulations. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 54 subjects were enrolled. No significant differences were found based on analysis of variance.  The mean values and 90% confidence intervals (CI) of test/reference ratios for these parameters of losartan as follows: Cmax 274.90 Vs 286.93 ng/mL (83.95 -113.69); AUC0-t 434.67 Vs 438.68 ng.hr/mL (93.30 -104.03); and AUC0-∞ 463.23 Vs 464.71 ng.hr/mL (94.65 -104.80) and for its active metabolite (losartan carboxylic acid) the mean values and 90% CI of test/reference ratios for these parameters  as follows: Cmax 572.63 Vs 543.82 ng/mL (96.87-109.37); AUC0-t 3987.89 Vs 4051.07 ng.hr/mL (93.48-104.22); and AUC0-∞ 4215.58 Vs 4271.67 ng.hr/mL (94.84-105.26). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.   Key Words: Bioequivalence, Losartan, losartan carboxylic acid, Pharmacokinetics.