| Purpose: This subject,applied pharmacokinetics theory,through the study and comparison of the pharmacokinetic behavior of a variety of effective components in the injection of Sheng Mai injection and Shen Mai Injection in patients with angina pectoris of Qi Yin deficiency,and to provide experimental basis for clinical treatment of the use of the injection and the Shen Mai injection.Material and method: 1.Using LC-MS detection of Qi and yin deficiency type of angina in patients with traditional Chinese medicine compound preparation for students of Shengmai injection and Shenmai injection effect components of ginseng saponin Rg1,ginsenoside Re,ginseng saponin Rb1,ginseng saponin Rb2,ginseng saponin Rc,ginsenoside Rd and Schisandra methanol blood drug concentration,and generation of the pharmacokinetic parameters were calculated using winnonlin software on the effective components of medicine.Chromatographic conditions are as follows: ZORBAX SB-C18 Synergi POLAR-RP chromatographic column?3.5 ?m,30 mm×2.16 mm,Agilent?;water?A?: acetonitrile?B?mobile phase gradient elution: 0-5 min 15-30?B?;5-18 mim 30?B?;18-19 min 30-100?B?;19-26 min 100?B?;flow: 0.3 ml / min,the column temperature: 40 ?;sample size: 10 ?L;Mass spectrometry conditions are as follows: ESI ion source;Gas Flow 9 L/ml,Gas Temp 350 ?,Nebulizer 40 psi,Capillary 4000 V;Positive ion mode detection,scanning mode for selective reaction monitoring?SIM?;ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,ginsenoside Rb2,ginsenoside Rc,ginsenoside Rd,and schisandrin are used for quantification of the ions.m/z: the parent ions were 823.5,969.6,1131.6,1101.7,1101.7,969.6,455.3 respectively;Fragmentor were 300,320,380,340,320,320,190 respectively;The internal standard of diazepam,m/z:the parention was 285.0,Fragmentor 165;scan time for 200 ms.2.The design method of random,open,parallel and controlled experiment was adopted.Recruitment will meet the inclusion criteria of 20 famous Yin deficiency card chronic,stability,fatigue angina patients were divided into two groups randomly, each group of 10 people,with the same dose administration.Each of the subjects were intravenously infusion of the test preparation?Shengmai injection 60 ml and 5% glucose injection 100 ml?or reference preparation?Shenmai injection 60 ml and 5% glucose injection 100 ml?,parallel control.Results: 1.The application of LC-MS method was developed for detection the blood concentration of plasma of patients with angina with Qi Yin deficiency in Shengmai injection and Shenmai injection on the effect of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,ginsenoside Rb2,ginsenoside Rc,ginsenoside Rd and Schizandrol.The detection of endogenous substances in plasma on plasma samples without interference,the linear range of the standard curve were 1 1000,1 1000,2 10000,0.5 10000,1 10000,2 1000 and 0.25500 ?g/L,the lower limit of quantification was1 ?g/L,1 ?g/L,2 ?g/L,0.5 ?g/L,1 ?g/L,2 ?g/L,0.25 ?g/L?S/N>10?.Batch and inter batch RSD were less than 15%,room temperature,repeated freezing and thawing,and long-term freezing conditions of RSD were less than 15%,indicating that the method is in accordance with the requirements of biological sample analysis.2.Intravenous infusion of Sheng Mai injection and Shen Mai Injection in patients with angina pectoris,and statistical analysis of pharmacokinetics by Win Nonlin.The pharmacokinetic parameters of the Sheng Mai injection were respectively: ginsenoside Rg1(Tmax:1.200 ± 0.350 h,t1/2 :19.758 ± 36.894 h,Cmax:229.945 ± 74.441?g / L,AUC0-144:1082.777 ± 1892.670 ?g·h/L,AUC0-?:1580.994 ± 3149.190 ?g·h/L),ginsenoside Re(Tmax:3.217 ± 4.479 h,t1/2 :115.386 ± 153.620 h,Cmax:78.862 ± 27.877 ?g / L,AUC0-144 :438.319 ± 486.698 ?g ·h / L,AUC0-?:1727.514 ± 2033.578 ?g·h/L),ginsenoside Rb1(Tmax:1.500 ± 0.333h?t1/2:75.741 ± 38.61439.728±10.774 h,Cmax: 2899.214 ± 885.503 ?g / L,AUC0-144 :122271.167 ± 22889.234 ?g·h/L?AUC0-?:170801.265 ± 31056.793 ?g·h/L),ginsenoside Rb2(Tmax:1.550 ± 0.369 h,t1/2 :33.925 ± 14.465 h,Cmax:747.030 ± 264.589 ?g / L,AUC0-144 :19141.538 ± 6641.604 ?g ·h / L,AUC0-?:21423.150 ± 9042.153 ?g·h/L),ginsenoside Rc(Tmax:2.117 ± 1.921 h,t1/2 :61.327 ± 21.685 h,Cmax:1541.776 ± 527.365 ?g/L,AUC0-144:59672.814 ± 16298.381 ?g·h/L,AUC0-?:73684.336 ± 19905.891 ?g·h/L),ginsenoside Rd(Tmax:1.400 ± 0.211 h,t1/2 :39.595 ± 25.991 h,Cmax:556.968 ± 210.551 ?g / L,AUC0-144 :6676.965 ± 2349.680 ?g ·h / L,AUC0-?:7649.501 ± 2885.632 ?g·h/L)and Schizandrol(Tmax:6.350±15.226 h,t1/2 :327.621±471.393 h,Cmax:13.861±2.377 ?g / L,AUC0-144 :546.936±395.365 ?g ·h / L,AUC0-?:2748.538±3672.340 ?g·h/L);The pharmacokinetic parameters of the Shen Mai injection were respectively: ginsenoside Rg1(Tmax:1.367 ± 0.255 h,t1/2 :16.040 ± 16.898 h,Cmax:424.376 ± 151.650 ?g/ L,AUC0-144:1117.036 ± 809.270 ?g·h/L,AUC0-?:1419.509 ± 940.391 ?g·h/L),ginsenoside Re(Tmax:1.917 ± 1.994 h,t1/2 :50.753 ± 55.946 h,Cmax:112.315 ± 41.591 ?g / L,AUC0-144 :797.105 ± 771.897 ?g ·h / L,AUC0-?:1543.766 ± 1586.896 ?g·h/L),ginsenoside Rb1(Tmax:1.575 ± 0.154 h?t1/2:48.618 ± 16.187 h,Cmax:3466.041 ± 468.337 ?g / L,AUC0-144 :125201.709 ± 45518.476 ?g·h/L?AUC0-?:146758.683 ± 54442.876 ?g·h/L),ginsenoside Rb2(Tmax:1.583 ± 0.152 h,t1/2 :42.909 ± 22.124 h,Cmax:952.605 ± 178.680 ?g / L,AUC0-144 :25794.662 ± 10324.596 ?g ·h / L,AUC0-?:29262.781 ± 10716.040 ?g·h/L),ginsenoside Rc(Tmax:1.583 ± 0.152 h,t1/2 :63.147 ± 12.084 h,Cmax:1960.461 ± 389.268 ?g/L,AUC0-144:78294.566 ± 27885.287 ?g·h/L,AUC0-?:99944.843 ± 37502.321 ?g·h/L)and ginsenoside Rd(Tmax:1.583 ± 0.152 h,t1/2 :51.340 ± 34.596 h,Cmax:494.512 ± 110.238 ?g / L,AUC0-144 :5801.599 ± 3559.808 ?g ·h / L,AUC0-?:7197.757 ± 4461.257 ?g·h/L).3.20 subjects were divided into two groups,each group were intravenously injected with intravenous injection of Sheng Mai injection and Shen Mai injection,of Ginsenoside Rg1?Re?Rb1?Rb2?Rc?Rd and Schizandrol blood drug concentration time curve by computer simulation.The results show that between the two preparations except ginsenoside Rd,Cmax were different?P < 0.05?;The AUC and clearance rate of ginsenoside RC had differences?P < 0.05?;The Tmax of ginsenoside Rd had difference?P < 0.05?;other pharmacokinetic parameters had no significant difference?P > 0.05?.Conclusion: 1.The application of LC-MS method for the detection of the content of effective components of ginseng saponin Rg1,ginsenoside Re,ginseng saponin Rb1,ginseng saponin Rb2,ginseng saponin Rc,ginsenoside Rd and schizandrin in the injection of Sheng Mai injection and Shen Mai injection in the plasma of patients with angina pectoris,and meet the requirements of biological sample detection.2.Model group of angina pectoris,The Cmax of both the effect of Sheng Mai injection and Shen Mai injection of ginseng saponin Rg1,ginsenoside Re,ginseng saponin Rb1,ginseng saponin Rb2,ginseng saponin Rc,ginsenoside Rd and schizandrin were different?P < 0.05?.AUC and clearance rate of ginseng saponin Rc were different?P?0.05?;The Tmax of ginsenoside Rd was different?P < 0.05?;Other pharmacokinetic parameters were not significantly different. |
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