Quantitative analysis of trazodone in human plasma by using HPLC-fluorescence detector coupled with strong cation exchange chromatographic column: application to a pharmacokinetic study in Chinese healthy volunteers.

A simple, selective, and sensitive high performance liquid chromatography (HPLC) procedure has been developed for determination of trazodone in human plasma. Prazosin was employed as the internal standard (IS). Sample preparation involved liquid-liquid extraction by methyl tert-butyl ether after alkalinization with ammonia. The HPLC separation was performed on a CAPCELL PAK SCX column (250mm×4.6mm, 5.0µm, Shiseido, Japan) with a mobile phase of acetonitrile/80mmol/L ammonium phosphate (pH adjusted to 6.0) (60:40, v/v) at a flow rate of 1.2mL/min. The peaks were detected by using fluorescence detector (excitation wavelength 320nm and emission wavelength 440nm). The extraction recovery was 72.6-88.3% and the method was over the concentration range of 5.0-2486ng/mL with a lower limit of quantitation (LLOQ) of 5.0ng/mL using 300µL of plasma. The intra- and inter-day accuracy of the method at three concentrations ranged from 96.7% to 104.2% for trazodone with precision of 2.9-3.7%. This validated method was successfully applied to a pharmacokinetic study enrolling 12 Chinese volunteers administered a single oral trazodone hydrochloride extended-release tablet of 75mg.

Unexpected effect of concomitantly administered curcumin on the pharmacokinetics of talinolol in healthy Chinese volunteers.

OBJECTIVE: To investigate the effect of concomitantly administered curcumin on the pharmacokinetics of the beta1 adrenoceptor blocker talinolol. METHODS: The study was conducted in a self-controlled, two-period experiment with a randomized, open-labeled design, using 12 healthy volunteers and a wash out period of 1 week between the administration of a single oral dose of 50 mg talinolol and the concomitant administration of curcumin (300 mg day(-1) for 6 days) and a single oral dose of 50 mg talinolol on the seventh day. Concentrations of talinolol were measured in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry. Non-compartmental analysis was used to characterize talinolol plasma concentration-time profiles, all pharmacokinetic parameters were calculated using DAS: (ver. 2.0) software, and comparisons of mean values were analyzed by the Wilcoxon signed rank test. Differences were considered to be significant at p < 0.05 (two-sided test). RESULTS: The consumption of curcumin for 6 days reduced the area under the curve (AUC) from predose to infinity (AUC(0-infinity)) of talinolol from 1860.0 +/- 377.9 to 1246.0 +/- 328.2 ng x h mL(-1), the highest observed concentration values (C(max)) were significantly decreased from 147.8 +/- 63.8 to 106.4 +/- 39.9 ng mL(-1), and the CL/F was increased from 27.9 +/- 5.5 to 43.1 +/- 13.4 L x h(-1) (p < 0.05). There was no significant difference in sampling time for C(max) (t(max)) and elimination half-life (t(1/2)) values between the two periods (p > 0.05). The interindividual variability in AUC(0-60) and C(max) of talinolol was comparable in two study periods; the coefficient of variance (CV) of AUC(0-60) and C(max) was 26 and 40% after curcumin versus 21 and 43% after talinolol alone, respectively. CONCLUSION: We suggest that the reduced bioavailability of talinolol is most probably due to the low intraluminal curcumin concentration, or possibly due to the upregulation of further ATP-binding cassette transporters, such as MRP2, in different tissues.