Isocorynoxeine is one of the main alkaloids in Chinese medicinal herbs, and has pharmacological activities such as antihypertensive, sedative, anticonvulsant, and neuronal protection. It is an effective component of Uncaria for the treatment of hypertension. In this study, we used a fast and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to detect isocorynoxeine in rat plasma and investigated its pharmacokinetics in rats. Six rats were given isocorynoxeine (15 mg/kg) by intraperitoneal (i.p.) administration. Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with positive ionization was applied. Intra-day and inter-day precisions (relative standard deviation, %RSD) of isocorynoxeine in rat plasma were lower than 12%. The method was successfully applied in the pharmacokinetics of isocorynoxeine in rats after intraperitoneal administration. The t1/2 of isocorynoxeine is 4.9 ± 2.1 h, which indicates quick elimination.
After [6,7-3H]-labelled norethisterone-3-oxime (NETO) and norethisterone-3-oxime acetate (NETO-AC) were given intravenously or orally through a nasal tube with 1 mg of respective unlabelled steroid to Rhesus monkey, serum samples were collected at various periods, and radioactivity was counted with or without reverse-phase HPLC separation in advance. Pharmacokinetics of NETO and NETO-AC were compared with those of norethisterone (NET) and norethisterone acetate (NET-AC) respectively which were studied in a similar experimental design. The results indicated that the serum concentration-time curve of NETO and NET could be adequately described by a two-compartment model. Average t 1/2 ka, t 1/2 alpha and t 1/2 beta with standard deviation for oral administration were 0.21 +/- 0.08 (h), 1.28 +/- 0.31 (h) and 10.01 +/- 4.59 (h) for NET and 0.37 +/- 0.81 (h), 0.90 +/- 0.26 (h) and 8.55 +/- 2.21 (h) for NETO respectively. NETO metabolized to NET which had a similar serum profile with its precursor. NET-AC also metabolized to NET, but more rapidly. It disappeared from blood 8-12 h after nasal feeding. NETO-AC was non-detectable at all when given orally because it metabolized immediately and extensively in the animal body. Its major metabolites, NETO, NET and NET-AC already appeared in the first blood sample drawn 15 min after administration. NETO-AC, when injected intravenously, declined abruptly and could not be detected 4 h later. Among the metabolites, only the deacetylated products (NET and NETO) reached relatively higher levels and sustained longer in blood.(ABSTRACT TRUNCATED AT 250 WORDS)
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