Characterization of phytoplankton functional types in the western Bay of Bengal: HPLC- and CHEMTAX-based approach.

This study investigates phytoplankton functional group variations in the western Bay of Bengal (WBoB) during the Spring Intermonsoon. Samples were collected from four cross-shore transects: Mahanadi (MN), Vamsadhara (VD), Godavari (GD), and Krishna (KS). East India Coastal Current and warm gyre influenced the southern transects (KS, GD), VD was experiencing moderate upwelling and MN was characterized by low salinity and oligotrophic conditions due to freshwater input. In response to hydrography, phytoplankton biomass and functional types differed within and between the transects. Chlorophyll-a (Chl-a) was spatially high in VD and low in MN. The subsurface Chlorophyll-a maxima (SSCM) was prominent and shallow in the MN and VD, compared to the southern transects. Total diagnostic pigments concentration was high in VD, followed by GD, KS and MN. Phytoplankton functional groups and each groups contribution to Chl-a was calculated through CHEmical Taxonomy (CHEMTAX). Diatoms and cyanophytes were the dominant functional types in the surface layers. Progressive shift from diatoms in the nearshore region to cyanophytes in the offshore was observed. The low saline and low-nutrient conditions were conducible for the growth of cyanophytes, while nutrient-rich optimum light layer of SSCM and upper layer of VD were favorable for diatoms. Cryptophytes contribution to Chl-a was higher in southern transects compared to the north. Prymnesiophytes and prasinophytes were high in the subsurface and deep layers could be due to their adaptions to light and nutrients. The present study highlights the significance of physical processes associated hydrography in structuring the phytoplankton functional types.

Identification and structural characterization of hydrolytic degradation products of alvimopan by LC/QTOF/MS/MS and NMR studies.

Alvimopan (ALV), a peripherally acting mu-opioid receptor (PAM-OR) antagonist used for the treatment of postoperative ileus, was examined for its degradation behaviour under different stress conditions. A total of five degradation products (DP1-DP5) were formed and identified using high-performance liquid chromatography (HPLC) method. Primarily, complete fragmentation pathways of the protonated drug and its degradation products (DP1-DP5) were elucidated by using liquid chromatography-mass spectrometry (LC/MS) and high-resolution mass spectrometry (HRMS) studies. Subsequently, three major degradation products (DP1-DP3) formed under acid hydrolytic stress conditions were isolated by preparative-high performance liquid chromatography (prep-HPLC) and subjected to nuclear magnetic resonance (NMR) experiments (1D and 2D NMR) for further confirmation of their structures. All the spectral data from LC/QTOF/MS/MS and NMR studies were used for the identification and structural characterization of degradation products (DP1-DP5).

LC/QTOF/MS/MS characterization, molecular docking and in silico toxicity prediction studies on degradation products of anagliptin.

Pharmaceutical drugs are potential molecules with specific biological activity. However, long-term use of these chemical molecules can affect the human physiological system because of their increased levels in the human body. Therefore, identification and structure elucidation of impurities or degradation products should be taken into consideration in order to assure drug safety. The present study assessed the degradation behaviour of dipeptidyl peptidase-4 (DPP-4) inhibitor anagliptin under different stress conditions as per ICH guidelines Q1A (R2) followed by elucidation of the structure of degradation products. All the stress samples were analysed by using UPLC/PDA. The superior separation of drug from its degradation products was attained with time programmed gradient elution on BEH C18 (100 mm × 2.1 mm, 1.7 µm) column using 10 mM ammonium formate (aqueous) and acetonitrile (organic) as the mobile phase components. All the degradation products of anagliptin were characterized using LC/QTOF/MS/MS. In addition, the activity and toxicity of degradation products were determined through molecular docking and in silico toxicity prediction studies, respectively. The developed UPLC/PDA method was validated as per ICH guidelines in terms of specificity, accuracy, precision, linearity and robustness.

In vitro and in vivo metabolic investigation of the Palbociclib by UHPLC-Q-TOF/MS/MS and in silico toxicity studies of its metabolites.

Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug. The in vitro metabolism studies were carried out by using microsomes (HLM and RLM) and S9 fractions (Human and rat). The in vivo metabolism of the drug was studied by administration of the PAB orally to the Sprague-Dawley rats followed by analysis of urine, faeces and plasma samples. The sample preparation includes simple protein precipitation (PP) followed by solid phase extraction (SPE). The extracted samples were analyzed by ultrahigh-performance liquid chromatography-quadruple time-of-flight tandem mass spectrometry (UHPLC/Q-TOF/MS/MS). A total of 14 metabolites were detected in in vivo matrices. The PAB was metabolized via hydroxylation, oxidation, sulphation, N-dealkylation, acetylation and carbonylation pathways. A few of the metabolites were also detected in in vitro samples. Metabolite identification and characterization were performed by using UHPLC/Q-TOF/MS/MS in combination with HRMS data. To identify the toxicity potential of these metabolites, in silico toxicity assessment was carried out using TOPKAT and DEREK softwares.

Proposal of degradation pathway with toxicity prediction for hydrolytic and photolytic degradation products of timolol.

Timolol (TIM) is a potent ß-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Development and validation of stability indicating LCMS assay method for TIM was accomplished coherent with ICH guideline. Successful chromatographic separation of TIM with its four degradation products was attained by using gradient elution mode on reverse phase column using ammonium acetate buffer, pH 4.6 as mobile phase A and organic solvent as the mobile phase B. Chromatographic conditions were set such as 1.0 mL min-1 flow rate, 20 µL injection volume, 30 °C column temperature and 320 nm detection wavelength. Four major degradation products obtained from hydrolysis and photolysis, were identified and characterized with the combination of liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS/MS) and accurate mass measurements. Degradation pathways were identified based on a comparison of the fragmentation pattern of the [M+H]+ ions of TIM and its degradation products. The method validation was performed as per ICH guideline Q2 (R1).

Forced degradation study of racecadotril: Effect of co-solvent, characterization of degradation products by UHPLC-Q-TOF-MS/MS, NMR and cytotoxicity assay.

Racecadotril, an enkephalinase inhibitor, was subjected to hydrolysis (acidic and alkaline), oxidation, photolysis and thermal stress, as per ICH specified conditions. The drug showed extensive degradation under acidic, basic hydrolysis and oxidative stress conditions whereas, it was stable under other stress conditions. A total of seven degradation products (DPs) were observed. The chromatographic separation was optimized on Acquity HSS Cyano (100×2.1mm, 1.8µ) column using 0.1% formic acid and acetonitrile as mobile phase in gradient mode. Six DPs were characterised by LC-MS/MS and DP1 by GC-MS. The major DPs (DP 2 and DP 5) were isolated and characterised by NMR. This is a typical case of degradation where co solvent methanol reacts with racecadotril leading to the formation of pseudo DPs, DP 6 and DP 5. Interestingly the MS/MS spectra of protonated drug, DP 4 and DP 7 showed product ions which were formed due to intramolecular benzyl migrations. In vitro cytotoxic activity studies on isolated DP 2 and DP 5 revealed that the former has no cytotoxic nature, whereas the latter has potential pulmonary and hepatic toxicity.

Effects of Green Tea on Streptococcus mutans Counts- A Randomised Control Trail.

CONTEXT: Mouth rinses have been in use from time immemorial as a supplement for routine oral hygiene. There are many number of mouth rinses currently available in the market in which many of them possess certain drawback, which has necessitated the search for alternate mouth rinses. AIM: The aim of the present study was to assess the effect of rinsing with green tea in comparison with chlorhexidine and plain water on Streptococcus mutans count. SETTING AND DESIGN: A short term, single blinded, cross over randomised control clinical trial. MATERIALS AND METHODS: Study includes a total of 30 subjects aged 20 to 25 years divided into three groups that is green tea group, chlorhexidine group, and plain water group. A baseline plaque samples were collected and under supervision of examiner all the subjects rinsed with 10 ml of respective solutions for one minute. Plaque samples were collected at five minutes after rinsing. All the 30 subjects were exposed to all the three rinses with a wash out period of seven days between the interventions. All the samples were sent to microbial analysis. RESULTS: Wilcoxon matched pair test and Mann-Whitney U test showed that both chlorhexidine and green tea significantly reduced Streptococcus mutans colony counts compared to plain water. CONCLUSION: The results of present study indicate that green tea mouth rinse proved to be equally effective compared to chlorhexidine which is considered as gold standard. This may also be a valuable public health intervention as it is economical and has multiple health benefits.

Pioglitazone:A review of analytical methods / 药物分析学报

Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. It selectively stimulates nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). It was the tenth-best-selling drug in the U.S. in 2008. This article examines published analytical methods reported so far in the literature for the determination of pioglitazone in biological samples and pharmaceutical formulations. They include various techniques like electrochemical methods, spectrophotometry, capillary electrophoresis, high-performance liquid chromatography, liquid chromatography-electrospray ionization-tandem mass spectrometry and high-performance thin layer chromatography.

Gunshot injuries to the extremities: experience of a U.K. trauma centre.

BACKGROUND: The Metropolitan Police figures suggest an increase in the incidence of injuries related to gun crime. We conducted a retrospective analysis of extremity gunshot injuries over a five-year period. Our aim is to report on our (1) incidence, (2) complications and (3) experience in treating these injuries. METHODS: Over a five-year period (1998-2002), 70 extremity gunshot injuries in 61 patients were identified from a trauma register and case notes reviewed retrospectively. The following were identified and analysed: type of injury (low or high-energy transfer), treatment (early/late), complications, patient demographics and compliance. RESULTS: There was a four-fold increase in incidence. Our incidence correlated well with The Metropolitan Police figures (r = 0.93). One-third of our injuries were managed non-operatively and on an outpatient basis. Complications were as follows: eight wound infections, one fracture non-union, one compartment syndrome, one vascular injury and five nerve injuries. Compliance was excellent for high-energy transfer injuries. CONCLUSION: Extremity gunshot injuries are on an increase in the United Kingdom highlighting the need for trauma surgeons' knowledge of the management of these injuries. Complications can be reduced to a minimum if the basic principles of management are strictly adhered to.