A liquid chromatography-tandem mass spectrometric method for the simultaneous quantitation of five components of Ixeris sonchifoliain (Bge.) Hance in rat plasma and its application to a pharmacokinetic study.

A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the simultaneous quantitation of five major active ingredients of Ixeris sonchifolia (Bge.) Hance in rat plasma has been developed and validated. After liquid-liquid extraction of 50μL plasma with ethyl acetate, analytes and internal standard (I.

Quantitation of bivalirudin, a novel anticoagulant peptide, in human plasma by LC-MS/MS: Method development, validation and application to pharmacokinetics.

A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and re-extracted with dichloromethane, after which the analyte and triptorelin as an internal standard (IS) were separated on a 300SB-C18 column (150 mm×4.6 mm i.

[Advance in studies on mechanism of active anti-tumor compounds from sponge].

With the decrease in land resources, marine resources open a new path for drug development, among which sponge is one of important marine biological resources. In recent years, many anti-tumor active compounds in new structures have been extracted and isolated from sponges. Targeted anti-tumor drugs from sponge become a new trend during the development of innovative drugs of marine resources.

Ultra-sensitive assay for paclitaxel in intracellular compartments of A549 cells using liquid chromatography-tandem mass spectrometry.

A high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of paclitaxel in intracellular compartments using docetaxel as internal standard (IS) has been developed and validated. A549 cancer cells (10(6)) were incubated with paclitaxel (2ng/mL) for up to 4h and then subjected to sequential extraction of cytosolic, membrane/organelle, nuclear and cytoskeleton soluble protein. Fractions were ultrasonicated to release protein bound paclitaxel after which drug was extracted using liquid-liquid extraction with diethyl ether:dichloromethane (2:1, v/v).

Bioequivalence of lamotrigine 50-mg tablets in healthy male volunteers: a randomized, single-dose, 2-period, 2-sequence crossover study.

Unlabelled: OBEJCTIVE: To compare the bioavailability of two 50-mg lamotrigine dispersible tablet formulations (Epilepax®, Ivax-TEVA Argentina Laboratories, Argentina, as a test formulation, and Lamictal®, GlaxoSmithKline, UK, as a reference formulation) in 24 healthy male volunteers.

Material And Methods: This study was a randomized, 2-period, 2-sequence crossover design that was open for subjects and investigators, but blind for the bioanalytical lab. Serum samples were obtained over a 120-h interval.

[Maturation of Cordyceps sinensis associates with alterations of fungal expressions of multiple Ophiocordyceps sinensis mutants in stroma of Cordyceps sinensis].

Objective: To examine maturational changes in expressions of Ophiocordyceps sinensis (O.sinensis) transition and transversion mutation genotypes in Cordyceps sinensis (C.sinensis) stroma.

Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study.

Background: This study investigated the effects of adding levomefolate calcium 0.451 mg (the calcium salt of L-5-methyltetrahydrofolate; Metafolin®) to an oral contraceptive containing ethinylestradiol (EE) 20 mcg/drospirenone (drsp) 3 mg on folate levels in healthy women seeking contraception.

Study Design: In this randomized, double-blind, multicenter US-based study, women (18-40 years) received 24 weeks (six cycles) of EE/drsp/levomefolate calcium or EE/drsp for 24 days followed by 4 days of levomefolate calcium alone or placebo, respectively.

[Detection of multiple Ophiocordyceps sinensis mutants in premature stroma of Cordyceps sinensis by MassARRAY SNP MALDI-TOF mass spectrum genotyping].

Objective: To examine the mutants of Ophiocordyceps sinensis (Os) in the stroma of premature Cordyceps sinensis (Cs).

Methods: Used MassARRAY single nucleotide polymorphism (SNP) MALDI-TOF mass spectrum genotyping, designed eight SNP extension primers on the basis of the scattered, multiple point mutations of known Os mutants within their internal transcribed spacer (ITS) segments, and examined the Os mutant genotypes relating to the GC-biased Os genotype (gb #AB067721) in premature Cs stroma.

Results: The two AT-biased genotypes and the GC-biased Os were simultaneously detected in premature Cs stroma.

[Brain functional imaging of frontotemporal lobar degeneration].

Frontotemporal lobar degeneration (FTLD) is one of the common diseases causing dementia by including degenerative changes within the brain. The clinical subtypes of FTLD comprise frontotemporal dementia (FTD), progressive nonfluent aphasia (PNFA), and semantic dementia (SD). In this review, the role of the brain functional imaging on diagnosing of FTLD is described.

Effect of arotinolol on left ventricular function in patients with idiopathic dilated cardiomyopathy.

Objective: To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy (IDCM).

Methods: Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol. The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only beta-blocker.

Does NT-proBNP remain a sensitive biomarker for chronic heart failure after administration of a beta-blocker?

Background: Beta-blockers exert complex effects on plasma N-terminal-pro-B-type natriuretic peptide (NT-proBNP) level.

Hypothesis: We aimed to investigate whether NT-proBNP was still able to mirror the severity of chronic heart failure and predict the prognosis of the disease after administration of a beta-blocker.

Methods: Forty-four patients with chronic congestive heart failure were enrolled in the study to randomly receive carvedilol or bisoprolol in addition to background therapy.

Sensitive quantification of ranolazine in human plasma by liquid chromatography--tandem mass spectrometry with positive electrospray ionization.

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method with positive electrospray ionization (ESI) was developed for the quantification of ranolazine in human plasma. After liquid-liquid extraction of ranolazine and internal standard (ISTD) phenoprolamine from a 100 microl specimen of plasma, HPLC separation was achieved on a Nova-Pak C(18) column, using acetonitrile-water-formic acid-10% n-butylamine (70:30:0.5:0.

Determination of aranidipine and its active metabolite in human plasma by liquid chromatography/negative electrospray ionization tandem mass spectrometry.

A simple, sensitive and rapid high-performance liquid chromatography/negative electrospray ionization tandem mass spectrometry method was developed and validated for the assay of aranidipine (AR) and its active metabolite (AR-M) in human plasma. Following a liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reversed-phase column and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M-H]- ions, m/z 387.0 --> 164.

[Clinical studies on level of N-terminal portion of brain natriuretic in the treatment and prognosis of Chinese patients with chronic left heart failure].

Objective: To study the relationship of the level of N-terminal portion of brain natriuretic (NT-ProBNP) with the treatment and prognosis of patients with acute attack of chronic left heart failure.

Methods: Patients (age range 18-80 years) with decompensated heart failure treated in the emergency department in Fuwai Hospital were included in this study. Dynamic changes of plasma levels of NT-ProBNP, angiotensin (AO), renin activity (PRA), angiotensin II (AT II) and aldosterone (ALD) were detected by enzyme linked immunoadsorbent assay (ELISA) before anti-cardiac failure treatment and 3-5, 5-7 days after the treatment.

Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba.

Objective: We evaluated the potential of 15 herbal medicines (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms and microsomal NADPH-CYP reductase.

Methods: The abilities of 1-1000 microg/mL of freeze-dried aqueous extracts of 15 HMs to inhibit phenacetin O-deethylation (CYP1A2), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), midazolam 1-hydroxylation (CYP3A4) and NADPH-CYP reductase were tested using human liver microsomes.

Results: The HMs Epimedii herba, Glycyrrhizae radix and Leonuri herba inhibited one or more of the CYP isoforms or NADPH-CYP reductase.

High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry.

The early detection of potential drug-drug interactions is an important issue of drug discovery that has led to the development of high-throughput screening (HTS) methods for potential drug interactions. We developed a HTS method for potential interactions of inhibitory drugs for nine human P450 enzymes using cocktail incubation and tandem mass spectrometry in vitro. This new method involves incubation of two cocktail doses and single cassette analysis.

Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro.

The stereoselectivity of the inhibitory interaction potential of lansoprazole and omeprazole isomers on six human cytochrome P450 forms was evaluated using human liver microsomes. Lansoprazole enantiomers showed stereoselective inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation, CYP2D6-catalysed dextromethorphan O-demethylation, CYP2E1-catalysed chlorzoxazone 6-hydroxylation and CYP3A4-catalysed midazolam 1-hydroxylation, whereas omeprazole only inhibited CYP2C19 stereoselectively. Of the P450 forms tested, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation was extensively inhibited by both the lansoprazole and omeprazole enantiomers in a competitive and stereoselective manner; the S-enantiomers of both drugs inhibited the hydroxylation more than the R-enantiomers.

Sensitive method for the determination of ibutilide in human plasma by liquid chromatography-tandem mass spectrometry.

A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for determination of ibutilide in human plasma. The analyte and internal standard sotalol were extracted from plasma samples by liquid-liquid extraction, and separated on a C(18) column, using acetonitrile-water-10% butylamine-10% acetic acid (80:20:0.07:0.

Lansoprazole enantiomer activates human liver microsomal CYP2C9 catalytic activity in a stereospecific and substrate-specific manner.

We recently proposed a possible stereoselective activation by lansoprazole of CYP2C9-catalyzed tolbutamide hydroxylation, as well as stereoselective inhibition of several cytochrome P450 (P450) isoforms. This study evaluated the effects of lansoprazole enantiomers on CYP2C9 activity in vitro, using several probe substrates. For tolbutamide 4-methylhydroxylation and phenytoin 4-hydroxylation, R-lansoprazole was an activator (140 and 550% of control at 100 microM R-lansoprazole, EC50 values of 19.

Simultaneous and continuous 24-hour plasma and cerebrospinal fluid leptin measurements: dissociation of concentrations in central and peripheral compartments.

The entrance of leptin into the central nervous system is of physiological relevance to the regulation of food intake, energy balance, and neuroendocrine function. To our knowledge, the relation between plasma and lumbar cerebrospinal fluid (CSF) leptin has not been examined across the 24-h period. To evaluate the relation between plasma and CSF leptin across the 24-h period, we studied simultaneous and continuous plasma and CSF leptin in nine subjects.

Stereoselective metabolism of lansoprazole by human liver cytochrome P450 enzymes.

The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNA-expressed cytochrome p450 (p450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Clint) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9- and 2.

Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin.

The ability of tricyclic antidepressants (TCAs) to inhibit phenytoin p-hydroxylation was evaluated in vitro by incubation studies of human liver microsomes and cDNA-expressed cytochrome p450s (p450s). The TCAs tested were amitriptyline, imipramine, nortriptyline, and desipramine. Amitriptyline and imipramine strongly and competitively inhibited phenytoin p-hydroxylation in microsomal incubations (estimated K(i) values of 5.

Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19.

Objective: To evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19.

Methods: A single oral dose of racemic lansoprazole (30 mg) was administered to 6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction-restriction fragment length polymorphism. The pharmacokinetic parameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration.