This paper describes a simple, rapid and sensitive liquid chromatography–tandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope (duloxetine d5) was used as an internal standard. Analyte and the internal standard were extracted from 100 μL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a C18 column by using a mixture of acetonitrile–5 mM ammonium acetate buffer (83:17, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r2≥0.99) over the concentration range of 0.05–101 ng/mL. Multiple-reaction monitoring mode (MRM) was used for quantification of ion transitions at m/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.

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Background: Despite its broad range of biological activities, use of curcumin is limited because of poor bioavailability. Here we report a novel curcumin formulation, Curcuwin Ultra? (CU?), with superior bioavailability as compared to 95% turmeric extract (TUR 1800). Methods: A randomized, double-blind, threetreatment, crossover oral bioavailability study was conducted in 24 healthy volunteers under fasting conditions. Subjects received a single dose of CU? 250 mg, 500 mg and 1900 mg of TUR1800 as per randomization schedule and blood samples were collected at 4 h and 0 h before dosing, and 0.5,

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Objectives Oral caffeine consumption results in rapid absorption with high blood levels followed by its sharp decline and is typically associated with reduction in beneficial effects of caffeine. To help extend the benefits of caffeine over a six-eight hour time period, we developed a new sustained release caffeine (SRC) formulation called XtenergyTM. The primary study objective was to compare the pharmacokinetic profile of SRC with immediate release caffeine (IRC). Secondary objectives were comparing the effects of SRC and IRC using caffeine research visual analogue scales (Caff - VAS) and evaluate its safety. Methods Twenty-six subjects were randomized to receive 200 mg of caffeine from SRC and IRC in a double blind, single-dose, two-period, crossover study in healthy subjects under fasting state. A washout duration of 7 days was followed between the two periods. Blood samples were collected at –4, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 & 24 hours in each period. Plasma caffeine levels were analysed using a validated LCMS/MS method. The changes in Caff-VAS for relaxed, alert, jittery, tired, tense, headache & overall mood from baseline (0) to 1, 2, 4, 6, 8, 10 & 12 hrs were evaluated. Results Twenty-four male subjects with mean age 32.71 ± 6.18 yrs completed the study. Median tmax was 325.53% higher (4.00 vs 0.94 hrs) and mean t1/2 was 21.34% higher (9.24 ± 4.56 vs 7.61 ± 3.98 hrs) for SRC (P < 0.05) compared to IRC, respectively. Geometric least squares means (GLSM) for AUC4–8 (11,673.52 vs 10,930.25 hr.ng/mL) & AUC6–12 (14,043.79 vs 11,432.41 hr.ng/mL) were 6.80% and 22.84% higher for SRC compared to IRC, respectively. SRC showed an equivalent total absorption as IRC based on 90% CI for AUC0–24 (43,312.07 vs 44,009.64 hr*ng/mL). SRC demonstrated significant effects (P < 0.05) on feelings of being more alert, less tired, better overall mood, less jittery & less tense compared to IRC. SRC was well tolerated with no adverse events. Conclusions The SRC formulation resulted in slow & sustained levels of plasma caffeine associated with feelings of being more alert, less tired, better overall mood, less jittery and less tense for longer time periods without any safety concerns. SRC could be beneficial for those involved in sustained operations demanding peak cognitive & physical performance for a longer time. Funding Sources OmniActive Health Technologies Ltd.