The liquid chromatograph?mass spectrometer consisted of an program chemical libraries along with a Finnigan TSQ Quantum Discovery max program equipped with an ESI probe. Lipophilic analytes were extracted from 0. 5 ml plasma, diluted with 10 l of diazepam remedy, with 4 ml ethyl acetate. The examples were centrifuged, evaporated and reconstituted within the mobile phase. Separation by chemical libraries chemical libraries on a column was followed by tandem mass spectrometric detection. The mass spectrometer was operated in positive ion mode and quantication was hence performed using selected reaction monitoring of the transitions of m/z 295277 for tanshinone IIA, m/z 297251 for cryptotanshinone, m/z 277249 for tanshinone, and m/z 285193 for the diazepam, respectively. This assay had a LLOQ of 0. 1 ng ml1, with intra and interday CV of tanshinone I, tanshinone IIA and cryptotanshinone being below 15%. Hydrophilic analytes were extracted from 0. 5 ml plasma, diluted with 10 l of protocatechuic acid solution, with 1 mol l1 HCl 30 l and then 4 ml ethyl acetate. The samples Dacomitinib were centrifuged, evaporated and reconstituted in the mobile phase. Separation by HPLC on C18 column was followed by electrospray ionization tandom mass spectrometric detection. The mass spectrometer was operated in bad ion mode and quantication was hence performed using selected reaction monitoring of the transitions of m/z 135. 0 for danshensu, 108. 0 for protocatechuic aldehyde and 108. 0 for IS, respectively. This assay had a LLOQ of 0. 1 ng ml1, and intra and interday CV of danshensu and protocatechuic aldehyde were below 15%. The plasma concentration?time data of analytes obtained HSP on days 1 and 16 were analyzed by model independent methods. The peak plasma drug concentration and time to Cmax were directly obtained from the plasma concentration?time data. The elimination half life was calculated as 0. 693/z, where z, the elimination rate constant, was calculated from the terminal phase of the semi log regression of the plasma concentration?time curve. The area under curve from time 0 to innity ) was estimated as AUC Ct/z, where Ct is the plasma concentration of the last measurable trial and AUC was calculated according to the linear trapezoidal rule. Total plasma clearance was calculated as dose/AUC. Descriptive statistics of pharmacokinetic parameters included geometric means, arithmetic means and standard deviation. 90% condence intervals were constructed for the ratios of with to without danshen treatment utilizing the log transformed data for the geometric least squares means of Cmax, HSP, t1/2 and CL/F. The resulting condence limits were altered by exponentiation and reported on the original measurement Dacomitinib scale. The statistical limits were set at 0. 80?1. 25. tmax was analyzed using Wilcoxons signed rank test. The DAS statistical analysis system was used. Each danshen capsule contained 0. 26 0. 05 mg cryptotanshinone, 0. 5 0. 1 mg tanshinone I and 0. 37 0. 04 mg tanshinone IIA, 0. 67 0. 01 mg protocatechuic aldehyde, 1. 7 0. 3 mg danshensu and 13. 5 1. 1 mg salvianolic acid B. CL/F was 48. 72 and 64. 69 t h1 and tmax was 0. 79 and 0. 92 h, t1/2 was 3. 05 and 3. 11 h, AUC was 353. 62 and 254. 96 ng ml1 h, respectively. Percentages of geometric LS means of Cmax, AUC, t1/2 and CL/F were 0. 689, 0. 739, 1. 018 and 1. 354, respectively. For 1 hydroxymidazolam, values of Cmax were 21. 42 and 16. 20 ng ml1, tmax was 0. 88 and 0. 96 h, t1/2 was 2. 70 and 2. 29 h, AUC was chemical libraries 74. 36 and 51. 24 ng ml1 h, respectively. Percentages of geometric LS means of Cmax, AUC, and t1/2 were 0. 764, 0. 750, and 0. 910, respectively. Percentages of geometric LS means of Cmax : Cmax and AUCmax : AUCmax were 1. 072 and 1. 035, Twelve healthy male Chinese subjects with a mean age of 24 years, a mean weight of 62. 8 kg and a mean height of 172 cm participated in this study. All subjects tolerated danshen and midazolam tablets well throughout the study. Total Dacomitinib pharmacokinetic data for both sampling periods were available for 12 subjects and were included in the pharmacokinetic analyses. Mean plasma midazolam and 1 hydroxymidazolam concentration?time proles before and after 14 days of danshen tablets are presented in Figures 1 and 2. Table 1 summarizes the pharmacokinetic parameters of midazolam and 1 hydroxymidazolam before and after 14 days of treatment with danshen tablets. For midazolam, values of Cmax were 113. 98 and 72. 50 ng ml1, respectively. Ninety percent CIs of Cmax and AUC of midazolam and 1 hydroxymidazolam were under the lower statistical limit set but 90% CIs of t1/2 were within the range of statistical limit set. A Wilcoxon signed rank test for midazolam and 1 hydroxymidazolam indicated that tmax was not signicantly dierent. Dacomitinib reached its maximum concentration at 4 h post dosing and reduced to about 1. 2 ng ml1 at 24 h post dosing. AUC and t1/2 of danshensu were 86. 2 22. 0 ng ml1 h, and 1. 20 0. 38 h, respectively. Cmax of cryptotanshinone, tanshinone I and tanshinone IIA were 0. 35 ng ml1, 0. 3 ng ml1 and 1. 0 ng ml1 at 0. 5 h after administration of danshen tablets, respectively.
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