Pharmacokinetic study of icariside II after a single dose administration of YiGu capsule in healthy Chinese volunteers.

To investigate the pharmacokinetic characteristics of icariside II after a single oral dose administration of YiGu Capsule in healthy -Chinese volunteers. 8 (4 female) healthy Chinese volunteers were involved and administrated for 15 doses of YiGu Capsule after fasting overnight. 4 ml of blood samples were collected at scheduled time before and after administration. Icariside II in human plasma was separated on a Agela Venusil XBP-C18 column (250 mm×4.6 mm, 5 µm), and eluted using acetonitrile-water (containing 0.1% formic acid) (70:30, V/V) as mobile phase. The analytes were detected with a -triple quad HPLC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 515.1 (precursor ion) to m/z 369.1 (product ion) for icariside II and m/z 321.0 (precursor ion) to m/z 275.0 (product ion) for lorazepam (internal standard).The plasma concentration of icariside II was determined by established HPLC-MS/MS method after disposition and its pharmacokinetic parameters were analyzed and evaluated by PK Solver Software (version 1.0). The Cmax, Tmax, t1/2, AUC0-24, AUC0-∞, MRT0-∞-1, 2.50±1.91 h, 7.61±2.81 h, 12.68±4.86 ng · mL-1 · h, 14.22±5.75 ng · mL-1 · h, 9.55±1.56 h, 12.81±7.94 L · h-1 and 121.70±32.70 L. The established HPLC-MS/MS method was sensitive, selective and rapid for icariside II pharmacokinetic study.

Bioequivalence of two misoprostol tablets in healthy Chinese female volunteers: a single-dose, two-period, double crossover study.

OBJECTIVE: To assess the bioequivalence of a new generic formulation of misoprostol (CAS 59122-46-2) 0.2 mg tablets (test) and the available branded tablet (reference) for the requirement of state regulatory criteria and the marketing of the test product in China. METHODS: A randomized-sequence, 2-period crossover study was conducted in 20 healthy Chinese female volunteers in the fasted state. Blood samples were collected at baseline and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 and 6 h after a single oral dose of 0.6 mg misoprostol test or reference, followed by a 7-day washout period. Misoprostol acid, the active metabolite of misoprostol, was determined by an HPLC-MS/MS method. Drug And Statistics 2.0 was used to calculate the pharmacokinetics parameters and assess bioequivalence of the 2 formulations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for Tmax, Cmax and AUC0-t were all within the range from 80% to 125%. Adverse events were monitored throughout the study based on clinical parameters and patient reports. RESULTS: The main pharmacokinetics parameters for the test and reference were as follows: t1/2 was (0.680 ± 0.371) h and (0.650 ± 0.264) h; Tmax was (0.415 ± 0.087) h and (0.399 ± 0.097) h; Cmax was (1.941 ± 0.417) ng/mL and (2.047 ± 0.397) ng/mL; AUC0-t was (1.535 ± 0.419) ng·h/mL and (1.652 ± 0.400)ng·h/mL, and the AUC0-∞ was (1.576 ± 0.465) ng·h/mL and (1.686 ± 0.396) ng·h/mL. The mean ratios (test: reference) for Cmax, AUC0-t, and AUC0-∞ were 95.3% ±13.2%, 92.65% ± 17.31%, and 93.61%±18.97%, respectively. No significant (p>0.05) differences in pharmacokinetic parameters were found between preparations, treatments and periods. CONCLUSIONS: This single-dose study in healthy Chinese fasted volunteers was shown that the misoprostol test and reference met the requirement of US and China regulatory criterion, and the test and reference were bioequivalent.

Determination of glycyrrhetic acid in human plasma by HPLC-MS method and investigation of its pharmacokinetics.

OBJECTIVE: To develop a high performance liquid chromatography mass spectrometry (HPLC-MS) method for the determination of the glycyrrhetic acid (GA) in human plasma and for the investigation of its pharmacokinetics after the oral administration of 150 mg diammonium glycyrrhizinate test and reference capsule formulations. METHODS: The GA in plasma was extracted with ethyl acetate, separated on a C(18) column with a mobile phase of methanol (5 mmol/L ammonium acetate)-water (85 : 15, V/V) and analysed using a MS detector. Ursolic acid (UA) was used as internal standard. The target ions were m/z 469.5 for GA and m/z 455.6 for UA, the fragment voltages were 200 V and 100 V for GA and UA respectively. RESULTS: The calibration curve was linear over the range of 0.5-200 ng/mL (r = 0.9974). The limit of quantification for GA in plasma was 0.5 ng/mL, the recovery was 76.0-80.0%, and the inter- and intra-day relative standard deviations (RSD) were <12%. The pharmacokinetic parameters of GA after a single dose of 150 mg diammonium glycyrrhizinate test and reference were as follows: the half life (t(1/2)) 9.65 +/- 3.54 h and 9.46 +/- 2.85 h, the time to peak concentration (T(max)) 10.95 +/- 1.32 h and 11.00 +/- 1.30 h, the peak concentration (C(max)) 95.57 +/- 43.06 ng/mL and 103.89 +/- 49.24 ng/mL; the area under time-concentration curve (AUC(0-48) and AUC(0-infinity)) 1281.84 +/- 527.11 ng.h/mL and 1367.74 +/- 563.27 ng.h/mL, 1314.32 +/- 566.40 ng.h/mL and 1396.97 +/- 630.06 ng.h/mL. The relative bioavailability of diammonium glycyrrhizinate capsule was 98.88 +/- 12.98%. CONCLUSION: The assay was sensitive, accurate and convenient, and can be used for the determination of GA in human plasma. Comparison of the bioavailability and pharmacokinetic profile of GA indicated that the test and reference capsules were bioequivalent.

Alternating layer and island growth of Pb on Si by spontaneous quantum phase separation.

Real-time in situ x-ray studies of continuous Pb deposition on Si(111)-(7x7) at 180 K reveal an unusual growth behavior. A wetting layer forms first to cover the entire surface. Then islands of a fairly uniform height of about five monolayers form on top of the wetting layer and grow to fill the surface. The growth then switches to a layer-by-layer mode upon further deposition. This behavior of alternating layer and island growth can be attributed to spontaneous quantum phase separation based on a first-principles calculation of the system energy.

Self-diffusion of small clusters on fcc metal (111) surfaces

We use ab initio density-functional theory supplemented with the embedded-atom method to study the self-diffusion of small clusters on the (111) surface of eight fcc metals. A zigzag motion is found to be important in the dimer and tetramer diffusions. The dimer diffuses by a zigzag and concerted motion. The trimer diffuses by a concerted three-atom motion. The tetramer diffuses through a zigzag motion where only two atoms move simultaneously in each step. Thus, instead of increasing, the migration energy is lowered (or stays constant) for the tetramer as compared to that for the trimer. This novel break of the upwards trend in migration energy is predicted to be a general phenomenon.