SIMULTANEOUS DETERMINATION OF ARTESUNATE AND AMODIAQUINE IN HUMAN PLASMA USING LC-MS/MS AND ITS APPLICATION TO A PHARMACOKINETIC STUDY

Objective: The objective of this research was to develop a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of artesunate and amodiaquine in human plasma.Methods: An analytical method based on LC-MS/MS has been developed and validated for the simultaneous determination of artesunate and amodiaquine in human plasma. Isotope-labeled compounds are used as internal standards for the quantification of these drugs. Analytes were extracted from the plasma using solid phase extraction (SPE) technique and chromatographed on a C8 column using an isocratic mobile phase composed of 0.1% ammonia solution and methanol (10:90, v/v). The mobile phase was pumped at a flow rate of 1.00 ml/min. A total of five analytical batches were generated for the calculation of intra-day and inter-day precision and accuracy during the entire course of validation.Results: The assay exhibits excellent linearity in the concentration range of 3.07–305.29 ng/ml for artesunate and 0.30–30.01 ng/ml for amodiaquine. Intra-day and inter-day precision and accuracy results are well within the acceptance limits. All the stability experiments were conducted in plasma samples and in neat samples are complying with the recent US FDA and EMEA guidelines.Conclusion: The proposed LC–MS/MS assay method is simple, rapid and sensitive enough for the simultaneous determination of artesunate and amodiaquine in human plasma. This method was successfully used to quantitate the in-vivo plasma concentrations obtained from a pharmacokinetic study and the results were validated by conducting incurred samples reanalysis (ISR).Â

<span style="font-size:10.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: HI;mso-bidi-font-weight:bold" lang="EN-US">Design and synthesis of new <i><span style="font-size:10.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-bidi-font-family:Mangal;mso-ansi-language:EN-US; mso-fareast-language:EN-US;mso-bidi-language:HI" lang="EN-US">N</span></i><span style="font-size:10.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-bidi-font-family:Mangal;mso-ansi-language:EN-US; mso-fareast-language:EN-US;mso-bidi-language:HI" lang="EN-US">'-substituted- 2-methylquinoline-3-carbohydrazides with antioxidant and antimicrobial activity</span></span>

930-935Ten new N'-substituted-2-methylquinoline-3-carbohydrazide scaffolds have been synthesized, characterized by their physical and spectral data (IR, 1H NMR, and MS) and screened for in vitro antimicrobial and antioxidant activities. Results clearly reveal that all the synthesized compounds possess in vitro <span style="mso-bidi-font-weight: bold">antioxidant activity at the tested dose as compared to the standard drug, ascorbic acid. From the results, it can be assumed that the presence of an electron donating group on the aromatic ring is an important requirement for the antioxidant activity of the synthesized compounds, <b style="mso-bidi-font-weight: normal">5a-j. The synthesized compounds have also been screened for antibacterial and antifungal activity against three different strains of Gram-positive (<i style="mso-bidi-font-style: normal">Bacillus subtilis, S. pyogens<span style="mso-bidi-font-style: italic">, and Staphylococcus aureus) and three strains of Gram-negative bacteria (<i style="mso-bidi-font-style: normal">Escherichia coli, Enterobactor aerogens and<span style="mso-bidi-font-style: italic"> Klebsiella pneumoniae) and two fungal strains (Candida albicans and <i style="mso-bidi-font-style: normal">Fusarium oxysporium). Some of the compounds are found to be active against all the tested organisms, but are equipotent and less active as compared to the standard drug streptomycin. Compounds 5b and 5j exhibit almost equipotent activity compared with the standard drug Itraconazol against fungal strain <i style="mso-bidi-font-style: normal">Fusarium oxysporium and another compound 5f which is <span style="mso-bidi-font-weight: bold">active against Candida albicans. </span

A rapid and sensitive liquid chromatographyâtandem mass spectrometric assay for duloxetine in human plasma: Its pharmacokinetic application

This paper describes a simple, rapid and sensitive liquid chromatographyâtandem mass spectrometry assay for the determination of duloxetine in human plasma. A duloxetine stable labeled isotope (duloxetine d5) was used as an internal standard. Analyte and the internal standard were extracted from 100 μL of human plasma via solid phase extraction technique using Oasis HLB cartridges. The chromatographic separation was achieved on a C18 column by using a mixture of acetonitrileâ5 mM ammonium acetate buffer (83:17, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r2â¥0.99) over the concentration range of 0.05â101 ng/mL. Multiple-reaction monitoring mode (MRM) was used for quantification of ion transitions at m/z 298.3/154.1 and 303.3/159.1 for the drug and the internal standard, respectively. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies. Keywords: Duloxetine in human plasma, Solid-phase extraction (SPE), Liquid chromatographyâtandem mass spectrometry, Method validation, Pharmacokinetic studie

Simultaneous Determination of Atorvastatin and Aspirin in Human Plasma by LC–MS/MS: Its Pharmacokinetic Application

A simple, rapid, and sensitive liquid chromatography tandem mass spectro-metric (LC–MS/MS) assay method has been developed and fully validated for the simultaneous quantification of atorvastatin and aspirin in human plasma using a polarity switch. Proguanil and furosemide were used as the internal standards for the quantification of atorvastatin and aspirin, respectively. The analytes were extracted from human plasma by the liquid–liquid extraction technique using methyl tert-butyl ether. The reconstituted samples were chromatographed on a Zorbax XDB Phenyl column by using a mixture of 0.2% acetic acid buffer, methanol, and acetonitrile (20:16:64, v/v) as the mobile phase at a flow rate of 0.8 mL/min. Prior to detection, atorvastatin and aspirin were ionized using an ESI source in the multiple reaction monitoring (MRM) mode. The ions were monitored at the positive m/z 559.2→440.0 transition for atorvastatin and the negative m/z 179.0→136.6 transition for aspirin. The calibration curve obtained was linear (r2 ≥ 0.99) over the concentration range of 0.20–151 ng/mL for atorvastatin and 15.0–3000 ng/mL for aspirin. The method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 3.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The proposed method was found to be applicable to clinical studies