Hydrastine pharmacokinetics and metabolism after a single oral dose of goldenseal (Hydrastis canadensis) to humans.

The disposition and metabolism of hydrastine was investigated in 11 healthy subjects following an oral dose of 2.7 g of goldenseal supplement containing 78 mg of hydrastine. Serial blood samples were collected for 48 hours, and urine was collected for 24 hours. Hydrastine serum and urine concentrations were determined by Liquid Chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters for hydrastine were calculated using noncompartmental methods. The maximal serum concentration (Cmax) was 225 ± 100 ng/ml, Tmax was 1.5 ± 0.3 hours, and area under the curve was 6.4 ± 4.1 ng ⋅ h/ml ⋅ kg. The elimination half-life was 4.8 ± 1.4 hours. Metabolites of hydrastine were identified in serum and urine by using liquid chromatography coupled to high-resolution mass spectrometry. Hydrastine metabolites were identified by various mass spectrometric techniques, such as accurate mass measurement, neutral loss scanning, and product ion scanning using Quadrupole-Time of Flight (Q-ToF) and triple quadrupole instruments. The identity of phase II metabolites was further confirmed by hydrolysis of glucuronide and sulfate conjugates using bovine ß-glucuronidase and a Helix pomatia sulfatase/glucuronidase enzyme preparation. Hydrastine was found to undergo rapid and extensive phase I and phase II metabolism. Reduction, O-demethylation, N-demethylation, hydroxylation, aromatization, lactone hydrolysis, and dehydrogenation of the alcohol group formed by lactone hydrolysis to the ketone group were observed during phase I biotransformation of hydrastine. Phase II metabolites were primarily glucuronide and sulfate conjugates. Hydrastine undergoes extensive biotransformation, and some metabolites may have pharmacological activity. Further study is needed in this area.

Analysis of goldenseal, Hydrastis canadensis L., and related alkaloids in urine using HPLC with UV detection.

A screening method was developed to extract and detect berberine and hydrastine alkaloids from goldenseal root powder and urine samples using HPLC with UV detection. The isocratic method was developed to detect alkaloids in 5 mL of urine prior to drug screening. Urine samples were spiked with the alkaloids at varying concentrations and extracted twice with 3:1 chloroform:2-propanol (CHCl(3):2-propanol). The extracts were combined, concentrated using nitrogen gas and the residue was then reconstituted with a mobile phase of acetonitrile:buffer (32:68). A 17 min isocratic run time was performed with a flow rate of 2.0 mL/min, and UV detection at 230 nm using a C(18) (250 mm × 4.6 mm) column at room temperature. The method showed good linearity for berberine (r(2)=0.9990) and hydrastine (r(2)=0.9983) over a range of 11.80 ng/mL to 17.64 µg/mL. The LOD for berberine in urine was 12.74 ng/mL and the LOD for hydrastine in urine was 54.48 ng/mL. Urine samples were spiked with goldenseal root powder and liquid extract as part of a blinded study to determine whether berberine and hydrastine alkaloids could also be extracted in vitro from goldenseal and show a presence in urine samples. Out of the 37 blinded urine samples extracted the two spiked samples were correctly identified based on the presence or absence of berberine and hydrastine. The results demonstrated that this method will enable laboratories to test for the herbal supplement in submitted urine samples prior to drug testing, avoiding false negative results.

Identification of dauricine and its metabolites in rat urine by liquid chromatography-tandem mass spectrometry.

A rapid, sensitive and specific liquid chromatographic-electrospray ionization (ESI) tandem ion trap mass spectrometric method has been developed for identification of dauricine and its metabolites in rat urine. Six healthy rats were administrated a single dose (100 mg/kg) of dauricine by oral gavage. The urine were sampled from 0 to 24 h and purified by using a C18 solid-phase extraction (SPE) cartridge, then the purified urine samples were separated on a reversed-phase C18 column using methanol/2 mmol/L ammonium acetate (70:30, v/v, adjusted to pH 3.5 with formic acid) as mobile phase and detected by an on-line MS detector. Identification and structural elucidation of the metabolites were performed by comparing their changes in molecular mass (Deltam) and full scan MS(n) spectra with those of the parent drug. At least eight metabolites (such as N-demethyl, dehydrogenate, demethoxyl, hydroxyl, glucuronide conjugated and sulfate conjugated metabolites) and the parent drug were found in rat urine.

[Tissue distribution and excretion of bromotetrandrine in rats].

AIM: To study the tissue distribution and excretion of bromotetrandrine (W198) in rats. METHODS: The concentrations of W198 in biological samples were determined by an HPLC method with UV detection. RESULTS: After a single i.v. dose of 20 mg x kg(-1) W198 in rats, the parent drug concentrations in tissues were higher than those in blood at the same time. Parent drug was mainly distributed in lung, kidney, heart and liver, the peak levels were attained at 0.25 h and decreasing at 2 h after dosing in most tissues. After a single iv dose of 20 mg x kg(-1) W198 in rats, the excretion of the parent drug in urine, feces and bile amounted to 0. 150%, 2.1% and 0.063% of the dose, respectively. CONCLUSION: W198 was mostly distributed in lung. The parent drug excretion was less than 3% via urine, feces and bile.

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.