Just Published: Journal of Chromatography B

A new issue of this journal has just been published. To see abstracts of the papers it contains (with links through to the full papers) click here:

Journal of Chromatography B
http://rss.sciencedirect.com/publication/science/7220

Selected papers from the latest issue:

Identification of the absorbed constituents after oral administration of Yuanhu Zhitong prescription extract and its pharmacokinetic study by rapid resolution liquid chromatography/quadrupole time-of-flight

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Ye Tao , Haiyu Xu , Shanshan Wang , Bing Wang , Yingchun Zhang , Weihao Wang , Bin Huang , Hongwei Wu , Defeng Li , Yi Zhang , Xuefeng Xiao , Yubo Li , Hongjun Yang , Luqi Huang
Yuanhu Zhitong prescription (YZP) is well known for its analgesic effect. However, its multiple bioactive components in vivo remain unclear. In this paper, a rapid resolution liquid chromatography/quadrupole time-of-flight (RRLC-ESI-Q/TOF) was employed to identify the bioactive components and partial metabolites after oral administration of YZP extracts. Meanwhile, a RRLC-ESI-Q/TOF method was established and validated for the simultaneous quantification of protopine, α-allocryptopine, tetrahydropalmatine, corydaline, tetrahyberberine and byakangelicin in rat plasma and applied for their pharmacokinetic research. The results showed that twenty-one bioactive components of YZP were absorbed into the blood circulation and seventeen components were detected in cerebrospinal fluid (CSF). Moreover, the kinetic profiles of six analytes were obtained and the results suggested that the six analytes peaked between 3.5 and 5.0h and C max ranged from 214.6 to 858.3. The works could provide key information for identification of bioactive constituents and understanding the metabolism as well as pharmacological actions for YZP.

Determination of paclitaxel in hyaluronic acid polymeric micelles in rat blood by protein precipitation-micelle breaking method: Application to a pharmacokinetic study

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Yanhua Liu , Jin Sun , He Lian , Xin Li , Wen Cao , Liming Bai , Yongjun Wang , Zhonggui He
An efficient dissociation of paclitaxel (PTX) from the home-made hyaluronic acid-octadecyl (HA-C18) polymeric micelles formulation in rat blood could not be achieved using previously published PTX analytical methods. So, we intended to develop the micelle-breaking method to determine paclitaxel encapsulated in the HA-C18 polymeric micelles in blood. The pretreatment method of blood samples adopted a simple one-step protein precipitation-micelle breaking process with methanol as micelle-breaking and protein precipitant solvents for complete extraction of PTX from HA-C18 micelles in blood. The micelle breaking efficiency of methanol was as high as 97.7%. Separation was carried out by gradient elution on an Acquity UPLC BEH C18 column with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile. A total single run time was as short as 3.0min. Detection was performed by triple-quadrupole mass spectrometry with positive electrospray ionization as source ionization in multiple-reaction monitoring mode at m/z 854.3→286.2 for PTX and m/z 808.5→527.3 for the internal standard, docetaxel. The method demonstrated good linearity at the concentrations ranging from 20 to 10,000ng/mL. The intra- and inter-day relative standard deviations were less than 9.9%. The mean extraction recoveries of PTX and IS were 94.7% and 87.5%, respectively. In summary, the methanol protein precipitation-micelle breaking method could extract PTX completely from the polymeric micelles. Finally, the method was successfully applied to a pharmacokinetic study of the home-made PTX-loaded HA-C18 polymeric micelles and Taxol solution after intravenous administration in rats.

Pressurized liquid extraction coupled with countercurrent chromatography for systematic isolation of chemical constituents by preprogrammed automatic control

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Yuchi Zhang , Liping Guo , Chunming Liu , Zi′ao Fu , Lei Cong , Yanjuan Qi , Dongping Li , Sainan Li , Jing Wang
Pressurized liquid extraction (PLE) coupled with high-speed countercurrent chromatography (HSCCC) via an automated procedure was firstly developed to extract and isolate ginsenosides from Panax quinquefolium. The experiments were designed under the guidance of mathematical model. The partition coefficient (K) values of the target compounds and resolutions of peak profiles were employed as the research indicators, and exponential function and binomial formulas were used to optimizing the solvent systems and flow rates of the mobile phases in a three-stage separation. In the first stage, ethyl acetate, n-butanol, and water were simultaneously pumped into the solvent separator at the flow rates 11.0, 10.0, and 23.0mL/min, respectively. The upper phase of the solvent system in the solvent separator was used as both the PLE solvent and the HSCCC stationary phase, followed by elution with the lower phase of the corresponding solvent system to separate the common ginsenosides. In the second and third stages, rare ginsenosides were first separated by elution with ethyl acetate, n-butanol, methanol, and water (flow rates: 20.0, 3.0, 5.0, and 11.0mL/min, respectively), then with n-heptane, n-butanol, methanol, and water (flow rates: 17.5, 6.0, 5.0, and 22.5mL/min, respectively). Nine target compounds, with purities exceeding 95.0%, and three non-target compounds, with purities above 84.48%, were successfully separated at the semipreparative scale in 450min. The separation results prove that the PLE/HSCCC parameters calculated via mathematical model and formulas were accurately and scientifically. This research has opened up great prospects for industrial automation application.

Classification of type 2 diabetes rats based on urine amino acids metabolic profiling by liquid chromatography coupled with tandem mass spectrometry

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Chunyan Wang , Hongbin Zhu , Zifeng Pi , Fengrui Song , Zhiqiang Liu , Shuying Liu
An analytical method for quantifying underivatized amino acids (AAs) in urine samples of rats was developed by using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Classification of type 2 diabetes rats was based on urine amino acids metabolic profiling. LC–MS/MS analysis was applied through chromatographic separation and multiple reactions monitoring (MRM) transitions of MS/MS. Multivariate profile-wide predictive models were constructed using partial least squares discriminant analysis (PLS-DA) by SIMAC-P 11.5 version software package and hierarchical cluster analysis (HCA) by SPSS 18.0 version software. Some amino acids in urine of rats have significant change. The results of the present study prove that this method could perform the quantification of free AAs in urine of rats by using LC–MS/MS. In summary, the PLS-DA and HCA statistical analysis in our research were preferable to differentiate healthy rats and type 2 diabetes rats by the quantification of AAs in their urine samples. In addition, comparing with health group the seven increased amino acids in urine of type 2 rats were returned to normal under the treatment of acarbose.

Rapid detection of bacteria in urine samples by the “three-plug-injection” method using capillary electrophoresis

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Lin Song , Wanchen Li , Guoxia Li , Dianjun Wei , Peng Ge , Guizhen Li , Fang Zheng , Xuguo Sun
This study explored a method that can rapidly detect bacteria in urine samples for the auxiliary determination of urinary tract infections (UTIs). Urine samples from patients with UTIs (230 cases) were obtained using aseptic technique. The urine biochemical assay was then carried out using an automated urine analyzer for all the urine samples. Bacterial species were identified by a combination of bacterial culture technique, morphological observation and the BACT-IST microbial identification/susceptibility analysis system. The most common seven species of bacteria in the study included Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis. Bacterial samples were suspended in sample buffer solutions and separated by the “three-plug-injection” method using capillary electrophoresis (CE). Each species of bacteria appeared as a bacterial peak. The mixture of the seven species also provided only one peak. Further analysis showed that the concentration limit for the “three-plug-injection” method is 10⁶ colony forming units (CFU)/mL, and there is a good linear relationship between the peak height and bacterial concentration (R ² =0.99). The effect of urine composition on CE results was also investigated. The results showed that urine composition, i.e., proteins, white blood cells (WBCs) and red blood cells (RBCs), affected the peak retention time but could not affect the separation of bacteria. The results demonstrated that the bacteria in urine samples can be detected within 10min by the “three-plug-injection” method using CE. The “three-plug-injection” method is therefore suitable for the rapid detection of organisms in clinical urine samples from UTIs.

High throughput liquid chromatography–tandem mass spectrometry assay for mercapturic acids of acrolein and crotonaldehyde in cigarette smokers’ urine

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Steven G. Carmella , Menglan Chen , Adam Zarth , Stephen S. Hecht
3-Hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) are urinary metabolites of the toxicants acrolein and crotonaldehyde, respectively. Virtually all human urine samples contain these metabolites, resulting from the action of glutathione-S-transferases on acrolein and crotonaldehyde, which are lipid peroxidation products, environmental and dietary contaminants, and constituents of cigarette smoke. We have developed a high throughput liquid chromatography–tandem mass spectrometry method for quantitative analysis of 3-HPMA and HMPMA in large numbers of small urine samples, as would be required in molecular epidemiology and clinical studies relating levels of these metabolites to cancer risk. Solid-phase extraction on mixed mode reverse phase-anion exchange 96-well plates provided sufficient purification for LC–MS/MS analysis, which was performed by auto-injection using a 96-well format, and resulted in clean, readily interpretable chromatograms, with detection limits of 4.5pmol/mL urine for 3-HPMA and 3.5pmol/mL urine for HMPMA. Accuracy was 92% for 3-HPMA and 97% for HMPMA while inter-day precision was 9.1% (coefficient of variation) for 3-HPMA and 11.0% for HMPMA. The method was applied to more than 2600 urine samples from smokers; mean levels of 3-HPMA and HMPMA were 4800±5358 (S.D.)pmol/mL and 3302±3341pmol/mL, respectively.

A simple and robust high-performance liquid chromatography coupled to a diode-array detector method for the analysis of genistein in mouse tissues

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): C. Tamames-Tabar , E. Imbuluzqueta , M.A. Campanero , P. Horcajada , M.J. Blanco-Prieto
A simple liquid–liquid extraction procedure and quantification by high-performance liquid chromatography (HPLC) method coupled to a diode-array detector (DAD) of genistein (GEN) was developed in various mouse biological matrices. 7-ethoxycoumarin was used as internal standard (IS) and peaks were optimally separated using a Kinetex C18 column (2.6μm, 150mm×2.10mm I.D.) at 40°C with an isocratic elution of mobile phase with sodium dihydrogen phosphate 0.01M in water at pH 2.5 and methanol (55:45, v/v), at a flow rate of 0.25mL/min. The injection volume was 10μL. In all cases, the range of GEN recovery was higher than 61%. The low limit of quantification (LLOQ) was 25ng/mL. The linearity of the calibration curves was satisfactory in all cases as shown by correlation coefficients >0.996. The within-day and between-day precisions were <15% and the accuracy ranged in all cases between 90.14% and 106.05%. This method was successfully applied to quantify GEN in liver, spleen, kidney and plasma after intravenous administration of a single dose (30mg/kg) in female BALB/C mice

Application of a high performance liquid chromatography–tandem mass spectrometry method for determination of buflomedil in human plasma for a bioequivalence study

12 August 2013, 08:39:58

Publication date: 15 September 2013
Source:Journal of Chromatography B, Volume 935
Author(s): Li Ren , Chun Yang , Yan Peng , Fan Li , Ying-hui Li , Heng Zheng
A rapid, simple and sensitive method based on ultra fast liquid chromatography–tandem spectrometry for the determination of buflomedil in human plasma has been developed and validated using carbamazepine as internal standard. After the precipitation of plasma sample with methanol, the analyte and IS were separated on an Ultimate C18 column (5μm, 2.1mm×50mm, MD, USA) with an isocratic mobile phase composed of acetonitrile and 5mM ammonium acetate in water (60:40, v/v) at a flow rate of 0.25ml/min. The analyte and IS were detected with proton adducts at m/z 308.3–237.1 and m/z 237.2–194.2 in positive ion electrospray ionization and multiple reaction monitoring acquisition mode, respectively. The lower limit of quantification of the method was 23.64ng/ml with a linear dynamic range of 23.64–1182ng/ml for buflomedil. The intra- and inter-batch precisions were less than 5.8%. The developed method was successfully applied to a bioequivalence study of two buflomedil hydrochloride preparations (150mg) in 22 healthy Chinese male volunteers. 

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Journal of Pharmaceutical and Biomedical Analysis

A new issue of this journal has just been published. To see abstracts of the papers it contains (with links through to the full papers) click here:

Journal of Pharmaceutical and Biomedical Analysis
http://rss.sciencedirect.com/publication/science/5266

Selected papers from the latest issue:

Identification and analysis of an impurity inducing clinical adverse effect in anti-adhesion carboxymethyl chitosan products

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Ming-Ming Yu , Ting-Fu Jiang , Yuan-Hong Wang , Dong-Yan Wang , Zhi-Hua Lv
Controlling and minimizing the adverse effects of drugs are the key issues in ensuring the safety of drug therapy. Carboxymethyl chitosan has been widely used as an anti-adhesion material. However, recently in China there have been several reported instances of conjunctival hyperemia associated with the use of carboxymethyl chitosan containing products. Through MS, FTIR, and GC analysis, an impurity, diglycolic acid, was discovered in carboxylmethyl chitosan products. Pharmacological tests further indicated diglycolic acid has antithrombogenicity properties and induces vasodilation, both of which can cause conjunctival hyperemia. Thus, through these tests it was ascertained that diglycolic acid was the culprit responsible for the adverse clinical effects. Next, emphasis shifted to trying to discover the mechanism responsible for generating the diglycolic acid. Under strong basic conditions, chloroacetic acid can generate glycolic acid, which, upon etherification, can become diglycolic acid. In order to avoid future adverse effects, we have established an HPLC method to detect and determine diglycolic acid in carboxymethyl chitosan products. This method is specific, accurate, and precise, and can be easily implemented into routine monitoring practice. Concurrently, a refined method has also been established in order to eliminate diglycolic acid from carboxymethyl chitosan.

Graphical abstract

An analytical approach based on ESI-MS, LC–MS and PCA for the quali–quantitative analysis of cycloartane derivatives in Astragalus spp.

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Assunta Napolitano , Seref Akay , Angela Mari , Erdal Bedir , Cosimo Pizza , Sonia Piacente
Astragalus species are widely used as health foods and dietary supplements, as well as drugs in traditional medicine. To rapidly evaluate metabolite similarities and differences among the EtOH extracts of the roots of eight commercial Astragalus spp., an approach based on direct analyses by ESI-MS followed by PCA of ESI-MS data, was carried out. Successively, quali–quantitative analyses of cycloartane derivatives in the eight Astragalus spp. by LC-ESI-MS ⁿ and PCA of LC-ESI-MS data were performed. This approach allowed to promptly highlighting metabolite similarities and differences among the various Astragalus spp. PCA results from LC-ESI-MS data of Astragalus samples were in reasonable agreement with both PCA results of ESI-MS data and quantitative results. This study affords an analytical method for the quali–quantitative determination of cycloartane derivatives in herbal preparations used as health and food supplements.

Graphical abstract

Optimisation methodology in the chiral and achiral separation in electrokinetic chromatography in the case of a multicomponent sample of dansyl amino acids

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Alessandro Giuffrida , Marianna Messina , Annalinda Contino , Vincenzo Cucinotta
Two different chiral selectors synthesised in our laboratory were used to test the possibility of separation for a sample consisting of ten different enantiomeric pairs of dansyl-derivatives of α-amino acids in electrokinetic chromatography. It was possible to observe all the peaks, though only partly resolved, due to the twenty analytes through an accurate strategy of choice of the experimental conditions. As a part of this strategy, a procedure of identification of the single peaks in the electropherograms called LACI (lastly added component identification) has been developed.

Graphical abstract

Quantitative capillary zone electrophoresis method for the precise determination of charge differences arising from the manufacture of heparan-N-sulfatase

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Daniel S. Roseman , Robert Weinberger
A rapid and reproducible high-resolution capillary zone electrophoresis (CZE) method capable of resolving the charge isoforms of intact heparan-N-sulfatase (HNS) has been developed to monitor the charge consistency across different batches of HNS. Separation was carried out using a bare fused silica capillary with a buffer system composed of 25mM Tris, pH 8.0. This CZE method allowed the separation and integration of 14 peaks, each arising from differences in the amount of sialic-acid and mannose-6-phosphate bearing glycoforms, which were confirmed using enzymatically modified samples. Standard conditioning and rinsing conditions of the capillary were used to achieve optimal repeatability. Excellent day-to-day precision was obtained for migration times of each peak relative to the electroosmotic flow marker with relative standard deviation (RSD)≤0.5%. The precision of the relative peak areas (peak area percentages) ranged from 0.6% to 2.8% RSD for the major isoforms (peaks 3–12), from 4.0% to 5.0% RSD for peaks 1 and 2, and from 7.4% to 23.2% RSD for peaks 13 and 14. The method was able to discriminate charge variation across different batches of HNS, including those with both significant and minor process changes.

Graphical abstract

Simultaneous investigation of sesquiterpenes, pyrrolizidine alkaloids and N-oxides in Butterbur (Petasites hybridus) with an offline 2D-combination of HPLC-UV and LC-MMI-ToF-MS

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Ahmet Alper Aydın , Thomas Letzel
With the worldwide rapid increasing interest in the use of natural products as dietary supplements, medical remedies and functional foods, it has been accepted that omitting the plant constituents with potential adverse effects was a huge fault of the past. Several countries developed regulations to limit the consumption of such products in the markets. Among these natural products, butterbur (Petasites) has been used for years as herbal supplement for its anti-spasmodic and anti-inflammatory effects. However, its hepatotoxic alkaloid content limits the direct usage. In this study, investigation of sesquiterpenes and pyrrolizidine alkaloids (PAs) together with their N-oxide forms has been conducted with an offline 2D-combination using high-performance liquid chromatography with UV detection (HPLC-UV) and liquid chromatography – multi mode ionization – time-of-flight mass spectrometry (LC-MMI-ToF-MS) for plant screening. The content has been qualitatively investigated to provide information on the constituents of the plant rhizomes extracted using ethanol. Besides the reported hepatotoxic and medically bio-active plant constituents, a strategy has been suggested for estimating the retention order and retention times with respect to calculated log D (distribution coefficient) and hydrophobicity distributions on C18 reversed-phase column when all standard compounds are not available in laboratory. In this sense, the influence of calculated log D and hydrophobicity distributions on retention time has been clarified via available PA and PA-N-oxide standards. The ethanolic extract of Petasites hybridus has been used for examination of the strategy in a real-sample model. Additionally, the advantages of the developed HPLC-UV and LC-MMI-ToF-MS combination have been discussed with respect to the presented results.

Graphical abstract

Application of an innovative design space optimization strategy to the development of LC methods for the simultaneous screening of antibiotics to combat poor quality medicines

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): J.K. Mbinze , A. Dispas , P. Lebrun , J. Mavar Tayey Mbay , V. Habyalimana , N. Kalenda , E. Rozet , Ph. Hubert , R.D. Marini
The poor quality of medicines is a crucial problem of public health. Therefore, it is important to have analytical tools to attend decisions of the legal authorities while combating this offense. In this context, the main objective of this study was to develop generic methods able to trace, screen and determine several antibiotics and common associated molecules by mean of liquid chromatographic techniques. For that purpose, an innovative Design Space optimization strategy was applied, targeting 16 antibiotics and 3 beta-lactamase inhibitors. The robustness of the developed method allowed using its use in an environment where operational factors such as temperature are not easy to control and eased its transfer to Ultra High Performance Liquid Chromatography. To demonstrate its ability to quantify the targeted molecules, the developed and transferred method was fully validated for two active ingredients commonly used in association, sulbactam and ceftriaxone, using the accuracy profile as decision tool. Based on this successful step, the method was then used for the quantitative determination of these two active ingredients in three pharmaceutical brands marketed in the Democratic Republic of Congo. Two out of the three pharmaceutical products did not comply with the specifications.

Graphical abstract

Characterization of currently marketed heparin products: Key tests for LMWH quality assurance

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Hongping Ye , Timothy K. Toby , Cynthia D. Sommers , Houman Ghasriani , Michael L. Trehy , Wei Ye , Richard E. Kolinski , Lucinda F. Buhse , Ali Al-Hakim , David A. Keire
During the 2007–2008 heparin crisis it was found that the United States Pharmacopeia (USP) testing monograph for heparin sodium or low molecular weight heparins did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS). In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to detect not only the contaminant OSCS, but also to improve assurance of quality and purity of these drug products. The USP monographs for the low molecular weight heparins (LMWHs) approved for use in the United States (dalteparin, tinzaparin and enoxaparin) are also undergoing revision to include many of the same tests used for heparin sodium, including; one-dimensional (1D) 500MHz ¹H NMR, SAX-HPLC, percent galactosamine in total hexosamine and anticoagulation time assays with purified Factor IIa or Factor Xa. These tests represent orthogonal approaches for heparin identification, measurement of bioactivity and for detection of process impurities or contaminants in these drug products. Here we describe results from a survey of multiple lots from three types of LMWHs in the US market which were collected after the 2009 heparin sodium monograph revision. In addition, innovator and generic versions of formulated enoxaparin products purchased in 2011 are compared using these tests and found to be highly similar within the discriminating power of the assays applied.

Graphical abstract

Analyses of marketplace tacrolimus drug product quality: Bioactivity, NMR and LC–MS

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Cynthia D. Sommers , Eric S. Pang , Houman Ghasriani , Robert T. Berendt , Vincent L. Vilker , David A. Keire , Michael T. Boyne II
Tacrolimus (FK506) is a potent, narrow therapeutic index, immunosuppressive drug used to avoid organ rejection in patients that have undergone organ transplantation. Recent clinical reports suggested a significant reduction in the tacrolimus concentration/dose ratio in the plasma of liver and kidney recipients when the reference listed drug was substituted with a generic drug. In response to these concerns about switching between tacrolimus from different approved manufacturers during treatment, the FDA initiated purity, potency and quality studies of the innovator and generic tacrolimus products available in the US marketplace. A combination of analytical methods, including mass spectrometry (LC–MS), nuclear magnetic resonance (NMR) and bioactivity assay were developed and validated to assess the quality of tacrolimus. These tests measured the identity, impurities and activity of tacrolimus from active pharmaceutical ingredient (API) sources and with formulated drug product from five different approved manufactures. In addition, some testing was performed on tacrolimus capsules obtained from a non US approved Indian source. The data obtained showed no discernible difference in the impurity profiles and potency between the generic and innovator tacrolimus products.

Graphical abstract

Characterization of degradation products of idarubicin through LC-UV, MSn and LC–MS-TOF studies

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Dheeraj Kaushik , Gulshan Bansal
Idarubicin was subjected to forced degradation under the ICH recommended conditions of hydrolysis, oxidation, dry heat and photolysis to characterize its possible impurities and/or degradation products. The drug was found unstable to acid hydrolysis at 85°C and to alkaline hydrolysis, and oxidation at room temperature. The hydrolytic and oxidative degradation products were resolved with gradient and isocratic elution, respectively on an Inertsil RP18 (250mm×4.6mm; 5μ) column with HCOONH4 (20mM, pH 3.0) and acetonitrile. The drug degraded to two products (O-I and O-II) in oxidative condition, two products (K-I and K-II) in alkaline hydrolytic, and one product (A-I) in acidic hydrolytic conditions. The purity of each in the LC-UV chromatogram was ascertained through LC-PDA analysis. The products were characterized through +ESI-MS ⁿ studies on the drug and LC–MS-TOF studies on the degraded drug solutions. Based on the multistage mass fragmentation pattern of idarubicin and accurate mass analysis of the degradation products, the O-I, O-II and A-I were characterized as desacetylidarubicin hydroperoxide, desacetylidarubicin and deglucosaminylidarubicin, respectively. The products K-I and K-II were not characterized due to their low concentrations and/or extremely weak ionization. The mechanisms of degradation of idarubicin to these products were proposed and discussed.

Graphical abstract

Reversed-phase thin-layer chromatography technique for the comparison of the lipophilicity of selected non-steroidal anti-inflammatory drugs

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Małgorzata Starek , Łukasz Komsta , Jan Krzek
The chromatographic behavior of a series of coxibs and oxicams, drugs from a group of non-steroidal anti-inflammatory drugs, was studied by reversed-phase thin-layer chromatography with binary mobile phases containing water and the organic modifiers: methanol, acetone, 1,4-dioxane, acetonitrile and 2-propanol. Linear relationships were obtained between the retention R M values of the compounds and the concentration of organic modifier in the mobile phase. Values of R M0, represent the theoretical R M values at 0% organic solvent in the mobile phase were calculated by extrapolation. These experimental lipophilicity values were correlated with lipophilicity (logP) from databases. The obtained results show that reversed-phase chromatography (experimental parameters) may be a good instrument for analytics in describing the lipophilic nature of investigated compounds as well as the activity.

Graphical abstract

Analysis and detection of the chemical constituents of Radix Polygalae and their metabolites in rats after oral administration by ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

08 August 2013, 21:21:53

Publication date: November 2013
Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 85
Author(s): Yun Ling , Zhixiong Li , Mingcang Chen , Zhaolin Sun , Mingsong Fan , Chenggang Huang
Radix Polygalae (RP), the dried root of Polygala tenuifolia Willd., is a well-known traditional Chinese medicine to mediate sedative, antipsychotic, cognitive improving, neuroprotective, and anti-inflammatory therapeutic effects on the central nervous system. In this work, ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-Q-TOF-MS/MS) was established for the separation and characterization of the chemical constituents in Radix Polygalae and their metabolites in rat plasma and urine after oral administration. Samples were separated on an Agilent Zorbax Eclipse Plus-C18 column (100mm×2.1mm, 1.8μm) with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase under gradient conditions. Overall, 50 compounds were characterized from the RP, 9 of which are to our knowledge reported for the first time. In vivo, 10 components and 2 metabolites were observed in rat plasma, and 27 components and 7 metabolites were detected in rat urine. The results from this work improve our understanding on the chemical constituents of RP and their metabolic profiling.

Graphical abstract

ICP Method Provides Broad Scan of Elemental Composition

A new analytical service note from Warwick Analytical Service (WAS) describes proprietary ICP-OES methodology developed by the company enabling them to provide simultaneous qualitative determination of up to 67 elements* in a single, cost effective measurement.
The WAS ‘Look & See ICP Scan Service’ provides information on elements present at 10-100 ppm right up to greater than 1% w/w. Measured intensities are compared to intensities of traceable standards to obtain the elemental levels in the unknown sample. Multiple wavelengths have been identified for each element to avoid errors due to the spectral interferences commonly found when using only a single analytical wavelength.

Operating in an ISO 17025 and GMP compliant environment following strict operating procedures ensures Warwick Analytical Service delivers top quality ICP data consistently. Equipped with modern high resolution ICP instrumentation and microwave digestion equipment - Warwick Analytical Service is able to offer its 'Look & See ICP Scan Service’ on almost any solid or liquid sample.
Warwick Analytical Service is a company dedicated to providing analytical excellence at a realistic cost. Through experienced staff, the latest analytical instrumentation and working closely with clients - WAS has established a strong reputation for informed personal service and delivering top quality data on time.

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Just Published: Microchemical Journal

A new issue of this journal has just been published. To see abstracts of the papers it contains (with links through to the full papers) click here:

Microchemical Journal
http://rss.sciencedirect.com/publication/science/6599

Selected papers from the latest issue:

Occurrence, transportation, monitoring and treatment of emerging micro-pollutants in waste water — A review from global views

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Jia-Qian Jiang , Z. Zhou , V.K. Sharma
This paper collects data from worldwide research groups and aims to critically review and analyse the advances of knowledge development in the area of occurrence, transportation, monitoring and treatment of emerging micro-pollutants from around the globe and to recommend the research needs in this research area. This review discovers that •A waste water treatment plant is one of pathways for micro-pollutants to transfer into surface waters; •Sample preparation, matrix effects and validation methods are challenges and more advanced analytical instrumentation and procedures are critical in analysing emerging micro-pollutants; •Traditional activated sludge and/or bio-filtration processes showed less efficiency to remove emerging micro-pollutants; •Advanced oxidation processes need to be validated for the efficiency and cost effectiveness; • More researches are needed to classify the type and toxicity of by-products resulting from the reactions between advanced oxidation processes and emerging micro-pollutants. The suggested future research needs from this review are challenges but provide us opportunities to effectively monitor and eliminate emerging micro-pollutants in the environment.

Selective separation of elements from complex solution matrix with molecular recognition plus macrocycles attached to a solid-phase: A review

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Ismail M.M. Rahman , Zinnat A. Begum , Hiroshi Hasegawa
Solid-phase extraction (SPE) approach was introduced approximately five decades ago, and until then development of SPE materials is seamlessly continued. Lately, the SPE-based research is increasingly focused in developing more explicit materials to achieve meticulous separation of elements from complex solution matrices with high concentrations of interfering ions. One group of SPE materials includes those with macrocyclic ligands immobilized on a solid-phase, which are capable of selective separation and pre-concentration of elements, and such selectivity in metal retention is generally termed as molecular recognition. In the process, the designed ‘host’ material possesses a high degree of recognition to specific elements or groups of elements called ‘guest’, and the recognition capability remains effective at the very low concentrations of the ‘guest’ species or when those present in complex matrices. The routes to the development of element-selective SPEs, the operating principles, applications and limitations are discussed in this review.

Determination of selenium compounds in food supplements using reversed-phase liquid chromatography–inductively coupled plasma mass spectrometry

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Yu-Jhe Hsieh , Shiuh-Jen Jiang
A reversed phase HPLC–ICP-MS method for the speciation of selenium compounds is described. Chromatographic separation was performed in a gradient elution mode using 2mmolL⁻¹ sodium 1-pentanesulfonate and 5mmolL⁻¹ citric acid in 3% methanol (pH2.70) and 5mmolL⁻¹ NaH2PO4 and 5mmolL⁻¹ citric acid in 3% methanol (pH2.77). The potentially interfering ³⁸Ar⁴⁰Ar⁺ and ⁴⁰Ar⁴⁰Ar⁺ at selenium masses of m/z 78 and 80 were reduced in intensity significantly by using 1.0mLmin⁻¹ CH4 as a reactive cell gas in the dynamic reaction cell. Calibration curves were linear in the range 0.1–10μgL⁻¹. The detection limits of the procedure were in the range of 0.04–0.07μgSeL⁻¹. This method has been applied to determine various selenium compounds in NIST SRM 1567a Wheat Flour and food supplements purchased locally. The accuracy of the method has been verified by comparing the sum of the concentration of individual species obtained by the present procedure with the total concentration of the element. The selenium compounds were quantitatively extracted with a mixture of Protease XIV and mobile phase solution in a microwave field at 37°C during a period of 30min. The extraction efficiency was better than 91%. The spike recoveries were in the range of 92–104% for all determinations. The electrospray ionization-mass spectrometer has been tested to identify the unknown selenium compounds detected in the food supplements. γ-glutamyl-methyl-Se-cysteine was identified in one brand of the Selenium Tablet.

Highlights

► Selenium compounds in food supplements were determined using HLPC–ICP-MS. ► Ar dimer ion interferences on Se determination were suppressed with CH4 as the DRC reaction gas. ► Selenium species were quantitatively extracted using microwave heating. ► γ-Glutamyl-methyl-Se-cysteine was identified in Selenium Tablet using ESI-MS/MS.

Transport of selenium species in Caco-2 cells: Analytical approach employing the Ussing chamber technique and HPLC-ICP-MS

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Denis Pick , Christian Degen , Matthias Leiterer , Gerhard Jahreis , Jürgen W. Einax
Essential trace elements such as selenium (Se) play a crucial role in health and diseases. Investigations of the transport and absorption of different Se species in vivo and in vitro consider only one Se species in a systematic manner. Thus, transport of four Se compounds (at concentrations of 100 and 400μgL⁻¹) namely selenite (SeO3 ²⁻), selenate (SeO4 ²⁻), selenomethionine (SeMet), and Se-methylselenocysteine (MeSEC) was compared using the Caco-2 cell line and the Ussing chamber system. For analytical measurements, an HPLC-ICP-DRC-MS method was developed and characterized. For the investigated Se species, limits of quantification were 0.5μgL⁻¹ while trueness was tested using the certified reference material SELM-1. Se species were added to the apical compartment of the Ussing chamber system either separately or simultaneously. Notably, no transport for SeO3 ²⁻ from apical to basolateral side was observed. Transport efficacy after 120min was the highest (9.1%) for SeMet in single species experiments, whereas SeO4 ²⁻ transport was the highest (7.9%) associated with simultaneous adding of Se species. Furthermore, changes in rank order of the apparent permeability coefficients Papp were obtained in mixture experiments as compared to the single species approaches. Finally, experimental data demonstrate alterations in transport of SeMet, MeSEC, and SeO4 ²⁻ suggesting interactions between Se species and changes in the transport behavior.

Highlights

► A simple and fast HPLC-ICP-DRC-MS method was developed for analysis of Se species. ► Se species were added to the Caco-2 cell model either simultaneously or separately. ► Selenite transport across Caco-2 cell monolayers is especially slow. ► Presence of other Se species influences the transport of selenate, SeMet, and MeSEC.

A portable fiber-optic Raman analyzer for fast real-time screening and identifying cocrystal formation of drug-coformer via grinding process

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Hong-Liang Lin , Gang-Chun Zhang , Po-Chun Hsu , Shan-Yang Lin
A portable Raman analyzer with a fiber-optic probe was first used to rapidly screen and identify the cocrystal formation between drug and coformer. Indomethacin (IMC) and anhydrous theophylline (TP) were selected as model drugs, but saccharin (SAC) and anhydrous citric acid (CA) were chosen as model coformers. The cocrystal formation that occurred in the solid-state IMC–SAC or TP–CA system via mechanical grinding process was investigated. Differential scanning calorimetry (DSC) was also used to investigate the possible cocrystal formation. The present study indicates that this new portable fiber-opticRaman spectroscopic technique was an easy and fast “real-time” method to screen and identify the progressive cocrystal formation in solid-state IMC–SAC or TP–CA system in the process of mechanical grinding by inserting the probe directly into the ground mixtures.

Post-fire study of the Brazilian Scientific Antarctic Station: Toxic element contamination and potential mobility on the surrounding environment

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Marcelo Braga Bueno Guerra , Elias Lima Neto , Marcelo Tesser Antunes Prianti , Edenir Rodrigues Pereira-Filho , Carlos Ernesto Gonçalves Reynaud Schaefer
We evaluated the new on site soil conditions and their potential risks immediately after a fire that completely destroyed the Brazilian Antarctic Station, on February 2012. The investigated variables were the concentration of potentially toxic elements (Cd, Cr, Cu, Mn, Ni, Pb, V and Zn) in soil samples collected close to the station and inside the burnt station's ruins. Soil samples collected 4years before the fire were used as reference samples for comparative purposes. Principal Component Analysis (PCA) and μ-X-Ray Fluorescence were used as preliminary tools to provide fast and reliable qualitative information about soil pollution. Inductively Coupled Plasma Optical Emission Spectrometry (ICP OES) was chosen for the quantitative determination of the chemical elements under study. A Toxicity Characteristic Leaching Procedure was applied to access the potential mobility of the chemical elements in the environment. We found high pseudototal concentrations of Cu, Pb and Zn in soils collected within the station's ruins reaching the alarming levels of 34,000±4,000, 13,700±500 and 42,200±1,700mgkg⁻¹, respectively. A point that deserves a close and special attention is the possible contamination of nearby lakes that supply the station with water, due to the high leachable Pb and Zn concentrations of the contaminated soil. Also, attention should be given to the possible development of melting channels carrying contaminated water to the coastal marine ecosystem. Due to its high risk of contamination, a complete clean-up procedure ought to be carried out, with barriers to avoid leaching/washing, removal of all debris and underlying soil, and careful disposal of the contaminated material, followed by remediation.

Highlights

► We evaluated the post-fire condition of soil samples near the Brazilian Antarctic Station. ► Copper, Pb and Zn presented alarming levels in the soil samples collected. ► μ-X-Ray Fluorescence in combination with chemometrics provides fast and reliable information. ► A complete clean-up procedure ought to be carried out to avoid leaching/washing.

Mercury species determination by task specific ionic liquid-based ultrasound-assisted dispersive liquid–liquid microextraction combined with cold vapour generation atomic absorption spectrometry

08 August 2013, 09:56:20

Publication date: September 2013
Source:Microchemical Journal, Volume 110
Author(s): Ewa Stanisz , Justyna Werner , Henryk Matusiewicz
Task specific ionic liquid-based ultrasound-assisted dispersive liquid–liquid microextraction (TSIL USA DLLME) combined with cold vapour atomic absorption spectrometry (CV AAS) for determination of mercury species in water and biological samples was developed. The proposed procedure was free of volatile organic solvents, and there was no need to use any dispersive solvents and complexing agents, in contrast to standard DLLME. Analytical signals were obtained without the back-extraction of the mercury species from the TSIL phase into an aqueous phase prior to their determination by CV AAS. The reducing agent Sn²⁺ could reduce Hg²⁺ and CH3Hg⁺ for determination of total mercury. Some essential parameters of the microextraction and cold vapour generation, such as the pH of sample solution, volume of the ionic liquid, ultrasonication time, cooling time, centrifugation time, matrix interferences and salt effect have been studied. Under optimal conditions, high extraction efficiency was achieved for the extraction of 1.0ngmL⁻¹ of Hg²⁺ and 5ngmL⁻¹ CH3Hg⁺ in 10.0mL of water solution employing 30μL of methyltrioctylammonium thiosalicylate as the extraction solvent. The enrichment factor for the method was 310 for Hg²⁺ and 200 for CH3Hg⁺. The detection limits were 0.03ngmL⁻¹ for Hg²⁺ and 0.4ngmL⁻¹ for CH3Hg⁺ respectively. The accuracy of the proposed method was evaluated by analysis of the Certified Reference Materials (NRCC DOLT-2, NIST 1643e). The method was applied to analysis of the tap, river, lake and sea water samples. The recoveries for reference materials and spiked samples were in the range of 95-103%.

Highlights

► The preconcentration of mercury species with TSIL USA DLLME is optimized. ► The determination by CV AAS in organic phase without back-extraction is proposed. ► The method requires low volume of sample and reagents. ► A low limit of detection, good precision and high enhancement factor were obtained. ► An application to mercury species determination in complex matrices was shown.

Oxford Instruments’ Asia Seminars attract record attendance

Oxford Instruments Plasma Technology has just completed its series of Asian seminars in Beijing, China and Hsinchu, Taiwan, attracting a record total attendance of over 250 people. The seminar in Beijing was co-hosted by the eminent Institute of Semiconductors, Chinese Academy of Sciences (IOS-CAS) one of the most important bases for the research and development of semiconductor science and technology in China, whilst its counterpart in Taiwan was co-hosted by ITRI, Taiwan’s leading non-profit R&D organisation with over 5,800 employees.

Both seminars featured a range of International and national speakers including Prof. Yang Fuhua from IOS-CAS in China and Prof. Chyi, Jen-Inn, Executive Vice President, National Applied Research Laboratories in Taiwan; with the talks covering a number of key areas including GaN on Si power device development, SiC wide bandgap semiconductors for power electronics applications and MEMS devices, processes and trends..

Dr. Shao-Chung Hsu, Executive Director of ITRI South Campus gave a welcome address at ITRI, and commented, “At ITRI we actively encourage our collaborations with leading industrial companies, and are delighted to join Oxford Instruments this week and hold such an informative conference.

Oxford Instruments has an excellent cleanroom facility established here at ITRI so it is fitting for us to host an event covering the wide range of applications that the Oxford Instruments systems can offer including MEMS, HBLED, ALD and III-V. Talks about the recent progress in their research and development and future trends in the fabrication and applications in micro and nano structures, gave the audience from academia and industry much opportunity for discussion. We hope to hold more events like this with Oxford Instruments at ITRI.”

Frazer Anderson, Business Group Director at Oxford Instruments Plasma Technology introduced the company at both seminars and summarises the company’s pleasure at the events’ success last week, “These technical seminars in China and Taiwan gave us and our audiences a great opportunity to spend time being updated by a wide range of eminent speakers, in a relaxed atmosphere where we can share experiences and learn more from our peers. As a company our ethos is to use innovation to turn smart science into world class products, and by working closely with partners at the top of their field and learning about their evolving requirements, their research and technological developments, we hope to achieve this.”