Identification and characterization of in vivo metabolites of asulacrine using advanced mass spectrophotometry technique in combination with improved data mining strategy.

Asulacrine (ASL) is a broad-spectrum, antitumor drug whose data are promising for the treatment of breast and lung cancers; however, a high incidence of phlebitis hampered its further development. Phlebitis is associated with generation of reactive species. Asulacrine donates electrons and produces oxidative stress in chemical reactions.

More accurate matrix-matched quantification using standard superposition method for herbal medicines.

Various analytical technologies have been developed for quantitative determination of marker compounds in herbal medicines (HMs). One important issue is matrix effects that must be addressed in method validation for different detections. Unlike biological fluids, blank matrix samples for calibration are usually unavailable for HMs.

The evaluation and implementation of Direct Analysis in Real Time quadrupole time-of-flight tandem mass spectrometry for characterization and quantification of geniposide in Re Du Ning Injections.

Rationale: The Direct Analysis in Real Time (DART) ionization source coupled with a quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) system has the capability to desorb analytes directly from samples from complex Chinese herbal preparations without sample cleanup or chromatographic separation.

Methods: In this work, a method based on DART/Q-TOF MS/MS has been developed for rapid determination of geniposide present in 'Re Du Ning Injections', a Chinese herbal preparation. The method has been evaluated for both qualitative and quantitative analysis of geniposide in Re Du Ning Injections.

Recent development in liquid chromatography/mass spectrometry and emerging technologies for metabolite identification.

Metabolism studies play a pivotal role in drug discovery and development since the active metabolites is critical to toxicological profile, efficacy and designing new drug candidates. From the instrumentation standpoint, liquid chromatography/mass spectrometry (LC/MS) has secured a central analytical technique for metabolite identification with the continuous developments and improvements in LC and MS technologies. Recently, a wide range of experimental strategies and post acquisition data processing and mining modes have emerged driven by the need to identify and characterize metabolites at ever increasing sensitivity and in ever more complex samples.

[Extraction, isolation and purification for ginkgolide B].

Objective: To establish a simple extraction, isolation and purification method for ginkgolide B from ginkgo leaf.

Method: The optimum conditions of extraction, isolation and purification were studied by taking the transfer rate of ginkgolide B as index.

Result: Ginkgo leaf was extracted with 70% ethanol for three times, the extracts were concentrated to remove ethanol and diluted by water till the crude drug density reached 0.

Qualitative and quantitative determination of complicated herbal components by liquid chromatography hybrid ion trap time-of-flight mass spectrometry and a relative exposure approach to herbal pharmacokinetics independent of standards.

To date, the pharmacokinetic research of herbal medicines (HMs) is still in its infancy and is facing critical technical challenges on the qualitative and quantitative analysis of complicated components from biological matrices. Additionally, the lack of authentic standards constitutes another bottleneck on assessing herbal pharmacokinetics. This present work contributes to the development of a powerful technical platform for both qualitative and quantitative pharmacokinetic analysis of herbal components, and a strategy of relative exposure that provides a practicable pharmacokinetic assessment independent of authentic standards, based on the use of liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF/MS).

Development of a systematic approach to identify metabolites for herbal homologs based on liquid chromatography hybrid ion trap time-of-flight mass spectrometry: gender-related difference in metabolism of Schisandra lignans in rats.

Metabolic research for herbal medicine (HM) is a formidable task, which is still in its infancy due to complicated components in HM, complex metabolic pathways, and lack of authentic standards. The present work contributes to the development of a powerful technical platform to rapidly identify and classify metabolites of herbal components based on a liquid chromatography hybrid ion trap time-of-flight mass spectrometry. Taking Schisandra lignans extract as an example, the metabolic studies were completed both in vitro and in vivo.

Influence of segmental and selected ion monitoring on quantitation of multi-component using high-pressure liquid chromatography-quadrupole mass spectrometry: Simultaneous detection of 16 saponins in rat plasma as a case.

Quadrupole (Q) mass spectrometers are the most popular analytical tools due to their reliability, effectiveness, and low cost. However, they are not suitable for quantitative analysis of multi-component since the sensitivity will get worse rapidly with the increasing number of m/z detected. The present work, for the first time, attempted to analyze of 16 saponins simultaneously using an approach of segmental and selected ion monitoring (SSIM) based on LC-Q/MS, and systematically investigated the influence of different SSIM modes on signal level/noise level (S/N), lower limits of quantification (LLOQ), upper limits of quantification (ULOQs), etc.

Rapid analysis of constituents of Radix Cyathulae using hydrophilic interaction-reverse phase LC-MS.

A hydrophilic interaction chromatography (HILIC) and reverse-phase liquid chromatography (RPLC) coupled with electrospray TOF MS method was developed for the analysis and characterization of constituents in the radix of Cyathula officinalis Kuan. Separation parameters of HILIC such as buffer pH, mobile phase strength, and organic modifier were evaluated. Fructose, glucose, and sucrose were identified by HILIC-ESI/TOF MS.

Application of a hybrid ion trap/time-of-flight mass spectrometer in metabolite characterization studies: structural identification of the metabolism profile of antofloxacin in rats rapidly using MSn information and accurate mass measurements.

We describe herein, a very effective way in the rapid identification of metabolites for antofloxacin based on a hybrid ion trap (IT)/time-of-flight (TOF) mass spectrometer technique. The purified samples were separated by a reversed-phase C18 column under a gradient elution, antofloxacin and its metabolites were detected by the on-line IT/TOF detector in scan mode. The identification of the metabolites and elucidation of their structure were performed by comparing the changes in molecular masses (DeltaM), calculating compound-based component by Formula Predictor software, and defining sites of biotransformation based upon mass shifts of diagnostic fragment ions according to the accurate MSn spectral information.

Organic solvent extraction and metabonomic profiling of the metabolites in erythrocytes.

We used erythrocytes as the model tissue to evaluate an optimal solution for the extraction of intracellular metabolites and time-dependent variation of the metabolome in living cells. Projection to latent structure (PLS) of the GC/MS and LC/MS data suggested that the most efficient solution for the extraction of metabolites from wet erythrocytes (50 mg) could be a methanol-chloroform-water mixture (950 microL, 700:200:50, v/v/v). PLS-discriminant analysis (DA) clearly profiled a time-dependent alternation of metabolic phenotype of erythrocytes.

Liquid chromatographic-mass spectrometry analysis and pharmacokinetic studies of erianin for intravenous injection in dogs.

The purpose of the present study was to examine the pharmacokinetic characteristics of erianin (2-methoxy-5-[2-(3,4,5-trimethoxyphenyl)-ethyl]-phenol, CAS 95041-90-0), a nature product extracted from Dendrobium chrysotoxum, having notable antitumour activity, after intravenous injection of erianin fat emulsion to beagle dogs. An HPLC-MS method was developed to analyze the erianin levels in dog plasma and validated in a pharmacokinetic study. Plasma profiles were obtained after intravenous injection of erianin fat emulsion at the doses 7.

Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC-APCI-MS: application of pharmacokinetic study in rats.

20(S)-Protopanaxadiol (PPD), the main metabolite of protopanoxadiol type ginsenosides (e.g. Rg3 and Rh2), is a very promising anti-cancer drug candidate.

Identification and quantification of 32 bioactive compounds in Lonicera species by high performance liquid chromatography coupled with time-of-flight mass spectrometry.

Flos Lonicerae, referred to the flower buds of several medicinal Lonicera species, is a commonly used traditional Chinese herbal medicine. A multi-component-assay quality control method, using high performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (HPLC-ESI/TOF MS), has been developed for the simultaneous identification and quantification of 32 bioactive compounds in Flos Lonicerae. The limits of detection (LOD) and quantification (LOQ) were in the range of 0.

Global analysis of metabolites in rat and human urine based on gas chromatography/time-of-flight mass spectrometry.

Sediment in urine may contain low-molecular-weight compounds that should be included in the analysis. To date, no systematic investigation has addressed this issue. We investigated three primary factors that influence the extraction efficiency of metabolites during preparation of urine samples for metabolomic research: centrifugation, pH, and extraction solvents.

Pharmacokinetic and absolute bioavailability study of total panax notoginsenoside, a typical multiple constituent traditional chinese medicine (TCM) in rats.

LC/ESI/MS method was employed for the pharmacokinetic evaluation of total panax notoginsenoside (TPNS) in rats. After oral or intravenous administration of TPNS at the dosage of 300.0 or 10.

Simultaneous determination of panax notoginsenoside R1, ginsenoside Rg1, Rd, Re and Rb1 in rat plasma by HPLC/ESI/MS: platform for the pharmacokinetic evaluation of total panax notoginsenoside, a typical kind of multiple constituent traditional Chinese medicine.

A platform for the pharmacokinetic study of multiple constituent traditional Chinese medicine was developed and validated. An HPLC/ESI/MS method was employed for the simultaneous determination of panax notoginsenoside R1, ginsenoside Rg1, Rd, Re and Rb1 in rat plasma. After the addition of digoxin as an internal standard (IS), rat plasmas were extracted with n-butanol saturated with pure water and all analytes were separated on a reversed-phased C(18) column with a mobile phase of acetonitrile-water (0.

[Study on the extraction recovery of ginsenoside Re in plasma by different solid-phase cartridges].

Objective: To optimize the solid-phase extraction method by comparison of the extraction recovery of ginsenoside Re plasma samples.

Method: After extracted by different solid-phase cartridges with water, acetonitrile, and different content methanol elution, the plasma samples were analyzed on an Zorbax SB-C18 column with acetonitrile-water gradient elution. From the recovery achieved, the best solid phase cartridge was found.

[Pharmacokinetics of oxymatrine and its metabolite in beagle dogs by LC-MS].

Objective: To establish LC-MS method in the determination of oxymatrine and its metabolite in plasma and investigate their pharmacokinetics in beagle dogs.

Method: Lichrospher C18 column (4.6 mm x 250 mm, 5 microm) was used as the analytical column maintained at 25 degrees C.

Simultaneous determination of oxymatrine and its active metabolite matrine in dog plasma by liquid chromatography-mass spectrometry and its application to pharmacokinetic studies.

A simple, rapid and reliable method was developed for the quantification of oxymatrine (OMT) and its metabolite matrine (MT) in beagle dog plasma using a liquid-liquid extraction procedure followed by liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) analysis. Extend-C18 column (2.1 mm i.

[Analysis of impurity in caderofloxacin].

Aim: To analyse the main impurity of caderofloxacin.

Methods: The impurity of caderofloxacin was analysed and determinated by RP-HPLC/ESI/MS with a Zorbax SB-C18 (150 mm x 4.6 mm ID, 5 microns) column.

[Study on the fingerprints of the alkaloids in Sophora flavescens].

Objective: To establish a method for HPLC fingerprint determination of the alkaloids in S. flavescens.

Method: RP-HPLC, linear gradient elution, LC/MS, etc.

[Analysis of the response factors of different quinolones detected by evaporative light-scattering detector].

Aim: To analyze the response factors of different quinolone antibiotics detected by evaporative light-scattering detector (ELSD).

Methods: The response factors of five different quinolones (enoxacin, levofloxacin, ciprofloxacin, lomefloxacin and gatifloxacin) detected by ELSD were determined by using a YMC-Pack ODS-AM cloumn (150 mm x 4.6 mm ID, 5 microns) as analytical column and 0.

[Determination of first-order structure of somatostatin by electrospray ionization mass spectrometry].

Aim: To determine the molecular weight and first-order structure of somatostatin.

Methods: The molecular weight of somatostatin was determined by electrospray ionization mass spectrometry. Somatostatin was deoxidized by 2-mercaptoethanol.

[Study on HPLC fingerprint of the triterpene acids in Poria cocos].

Objective: To establish a method for HPLC fingerprint determination of the triterpene acids in Poria cocos.

Method: RP-HPLC, linear gradient elution and LC/MS, etc. were used to optimize the fingerprint determination method, and identify the main peaks in the HPLC fingerprint.