A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the simultaneous determination of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone, the active components of Salvia miltiorrhiza in rat plasma, was developed. After liquid-liquid extraction with tariquidar as an internal standard, tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone were eluted from an Atlantis dC18 column within 5 min with a mixture of methanol and ammonium formate (10 mm, pH 6.5; 85:15, v/v). The analytes were detected by an electrospray ionization tandem mass spectrometry in the selected reaction monitoring (SRM) mode. The standard curves were linear (r=0.999) over the concentration range of 0.25-80 ng/mL for tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone in rat plasma. The coefficients of variation and the relative errors of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone for intra- and inter-assay at four quality control (QC) concentrations were 1.1-5.1% and -4.0-6.0%, respectively. The lower limit of quantification for tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone was 0.25 ng/mL from 100 microL of plasma. This method was successfully applied to the pharmacokinetic study of tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone after oral administration of PF2401-SF, the standardized fraction of Salvia miltiorrhiza enriched with tanshinone I, dihydrotanshinone I, tanshinone IIA and cryptotanshinone to male Sprague-Dawley rats.

Jaceosidin is an active component in Artemisia species as well as Eupatorium species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory, and antimutagenic activities. Jaceosidin was metabolized to jaceosidin glucuronide, 6-O-desmethyljaceosidin, hydroxyjaceosidin, 6-O-desmethyljaceosidin glucuronide, and hydroxyjaceosidin glucuronide in human liver microsomes. This study characterized the human liver cytochrome P450 (CYP) and UDPglucuronosyltransferase (UGT) enzymes responsible for the metabolism of jaceosidin. CYP1A2 was identified as the major enzyme responsible for the formation of 6-O-desmethyljaceosidin and hydroxyjaceosidin from jaceosidin on the basis of a combination of correlation analysis and experiments including immuno-inhibition, chemical inhibition in human liver microsomes, and metabolism by human cDNA-expressed CYP enzymes. Jaceosidin glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results suggest that the pharmacokinetics of jaceosidin may be dramatically affected by polymorphic CYP1A2, UGT1A1, and UGT1A7 responsible for the metabolism of jaceosidin or by the coadministration of relevant CYP1A2 or UGT inhibitors or inducers.

This study was first conducted to characterize the intravenous and oral pharmacokinetics of magnolin, a major pharmacologically active ingredient of Magnolia fargesii, at various doses in rats. Magnolin was administered to rats by intravenous injection (0.5, 1 and 2 mg/kg doses) and oral administration (1, 2 and 4 mg/kg doses), and serial plasma and urine samples were harvested. Magnolin concentrations were determined by a validated LC/MS/MS assay. After both intravenous and oral administration, the AUCs were linearly increased as the dose increased. Other pharmacokinetic parameters of magnolin (except the V ( ss ) after the intravenous administration) were also independent of the doses. The extent of absolute oral bioavailability ranged from 54.3-76.4% for the oral doses examined. Magnolin was considerably bound to rat plasma proteins and the binding value was constant (71.3-80.5%) over a concentration ranging from 500 to 10000 ng/mL. The pharmacokinetic parameters of magnolin were dose-independent after both intravenous and oral administration. When given orally, magnolin was rapidly absorbed.

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Changes in plasma level of arginine vasopressin (AVP), arterial pressure, and urine flow were studied before, during and after cardiopulmonary bypass (CPB) in 11 patients with congenital heart disease. Anesthesia was induced with thiopental sodium (3-5 mg/kg) and was maintained with enflurane (1.0-1.5%), 50% N2O in O2 and morphine (0.5 mg/kg). Concentration of plasma AVP increased slightly from 3.8 +/- 1.5 pg/ml after induction and increased 3-fold after sternotomy. Plasma AVP level increased to 132 +/- 26 pg/ml and 218 +/- 54 pg/ml after 5 and 60 min on CPB, respectively. When the circulation returned to normal, plasma AVP level decreased gradually but was still significantly higher at 24 hr (13.4 +/- 2.5 pg/ml). Marked osmolar diuresis was induced with mannitol in the priming solution used during the CPB: increases in urine flow, Na excretion and osmolar clearance. Possible mechanisms of marked increase in AVP release and differences of AVP responses during CPB reported by other investigators are discussed.