| Panaxsaponin C-K(20(S)-O-β-D-glucopgranose protopanoxadiol) have various Pharmacological activity to anti - mutant, inhibit cancer cell metastasis, cytotoxicity, induced apoptosis, and reverse drug resistance. In this study, the distribution, excretion studies of panaxsaponin C-K in rat were performed, which were based on the determinations of Panaxsaponin C-K in plasma, tissue, bile, urine and dung.A liquid chromatography and tandem mass spectrometry method has been developed for the determination of Panaxsaponin C-K in the various biological specimen. Its structural analogues glycyrrhetinic acid was used as the internal standard. After liquid-liquid extraction, samples were separated on a C18 column and the mobile phase consisted of methanol/acetonitrile (3:2, V) as a mobile phase A, and ammonium acetate buffer (10mmol/L) as the mobile phase B(gradient elution:0—2.5 min, A95%—B5%;2.6—3.5min , A50%—B50%,3.6—6min,A95%—B5 %). An API 4000 tandem mass spectrometer equipped with ESI (electrosprary ionization) was used as detector and was operated in the negative ion mode. Multiply reaction monitoring (MRM) using the precursor/product ion combinations of m/z 621.4—161.1 (C-K) and m/z 469.3—425.2 (internal standard, glycyrrhetinic acid) was used to quantify C-K. The assay was reproducible and linear for C-K in the range of 2.0-2.0×103ng·mL-1.The lower limit of quantification was 2.0 ng·mL-1. The accuracy, precision, sensitivity, specificity and linearity of this method satisfied the requirements of pharmaceutical analysis in biological samples.The distribution and elimination of Panaxsaponin C-K in rats was studied. The Panaxsaponin C-K concentration was high in the liver, pancreas, kidney and intestine, The elimination of Panaxsaponin C-K from the tissues was rapid. It was indicated that Panaxsaponin C-K did not readily accumulated in rat. Data of the urine and bile excretion indicated that only a small percent of C-K was excreted. The excretion of drug in urine, dung and bile amounted to only 0.0032%,5.37%(in 48 h)and 16.89% (in 24h)of the dosage. It is speculated that Panaxsaponin C-K may be metabolized such as protopanaxadiol and excretion.Danshensu is one of the active components in Salivia Miltiorrhiza which is a Chinese herbal preparation used widely in medical practice. A simple LC/MS/MS method was established to determine danshensu in animal plasma. The preclinical pharmacokinetics and absolute bioavailability of danshensu was studied by the validated LC-MS/MS method. The linear calibration curve was obtained in the concentration range of 2-400ng·mL-1.The lower limit of quantitation of danshensu was 2ng·mL–1. The inter- and infra-day precision (RSD) was less than 9%, and accuracy (relative error) was within士6.0%.The pharmacokinetic parameters were assessed by non-compartmental method using DAS2.0. The concentration in plasma-time curves were all fitted to two-compartment models. Comparison between AUC0-t after an oral administration and an i.v. administration indicated that the average absolute bioavailabilities of danshensu in dogs were 40%. After an oral and intravenous doses of 2mg/kg, T1/2 was23±0.20h和3.3±074h respectively. After oral administration the Tmax of was 1.0±0.32h,and after i.v. administration CL was 1.24±0.60ml·min-1·kg-1。...
|
PDF Full Text Request