Quantification of montelukast,a selective cysteinyl leukotriene receptor (CysLT1) antagonist in human plasma by liquid chromatography–mass spectrometry: validation and its application to a human pharmacokinetic study

A highly sensitive, rapid assay method has been developed and validated for the estimation of montelukast (MTK) in human plasma with liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive‐ion mode. Liquid–liquid extraction was used to extract MTK and amlodipine (internal standard, IS) from human plasma. Chromatographic separation was achieved with 10 mm ammonium acetate (pH 6.4): acetonitrile (15:85, v/v) at a flow rate of 0.50 mL/min on a Discovery HS C₁₈ column with a total run time of 3.5 min. The MS/MS ion transitions monitored were 586.10 → 422.10 for MTK and 409.20 → 238.30 for IS. Method validation and clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.25 ng/mL and linearity was observed from 0.25 to 800 ng/mL. The intra‐day and inter‐day precisions were 5.97–8.33 and 7.09–10.13%, respectively. This novel method has been applied to a pharmacokinetic study of MTK in humans. Copyright © 2009 John Wiley & Sons, Ltd.     

Stereoselective synthesis of umuravumbolide

An efficient stereoselective total synthesis of umuravumbolide has been developed. The key features of the synthesis include Jacobsen resolution, Wadsworth Emmons olefination and silyl-tethered ring closing metathesis.     

Analysis of the MAP/G a ,b /1/N Queue

The Markovian arrival process (MAP) is used to represent the bursty and correlated traffic arising in modern telecommunication network. In this paper, we consider a single server finite capacity queue with general bulk service rule in which arrivals are governed by MAP and service times are arbitrarily distributed. The distributions of the number of customers in the queue at arbitrary, post-departure and pre-arrival epochs have been obtained using the supplementary variable and the embedded Markov chain techniques. Computational procedure has been given when the service time distribution is of phase type.     

Synthesis and Characterization of Process Related Impurities of (±)‐Milnacipran

Milnacipran is a cyclopropane derivative, used as an anti depressant drug. During the process development of milnacipran, four process related potential impurities were detected in high performance liquid chromatography. All these impurities were identified, synthesized and subsequently characterized by their respective spectral data (IR, LC‐MS, ¹H NMR, and ¹³C NMR) as described in this article.     

Development and validation of a highly sensitive LC‐MS/MS method for simultaneous quantitation of nortriptyline and 10‐hydroxynortriptyline in human plasma: application to a human pharmacokinetic study

A highly sensitive and specific LC‐MS/MS method has been developed for simultaneous estimation of nortriptyline (NTP) and 10‐hydroxynortriptyline (OH‐NTP) in human plasma (250 µL) using carbamazepine as an internal standard (IS). LC‐MS/MS was operated under the multiple reaction‐monitoring mode using the electrospray ionization technique. A simple liquid–liquid extraction process was used to extract NTP, OH‐NTP and IS from human plasma. The total run time was 2.5 min and the elution of NTP, OH‐NTP and IS occurred at 1.44, 1.28 and 1.39 min, respectively; this was achieved with a mobile phase consisting of 20 mm ammonium acetate : acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a HyPURITY C₁₈ column. The developed method was validated in human plasma with a lower limit of quantitation of 1.09 ng/mL for both NTP and OH‐NTP. A linear response function was established for the range of concentrations 1.09–30.0 ng/mL (r > 0.998) for both NTP and OH‐NTP. The intra‐ and inter‐day precision values for NTP and OH‐NTP met the acceptance as per FDA guidelines. NTP and OH‐NTP were stable in a battery of stability studies, i.e. bench‐top, auto‐sampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in humans. Copyright © 2010 John Wiley & Sons, Ltd.     

A Novel Synthesis of Ketoprofen,Important Non-Steroidal Antiinflammatory Agent

The α-propionic acid moiety in. ketoprofen is attached through Wittig Homer reaction of ethyl-phosphono propionate on 3-benzyl cyclohexanone, prepared by G. reaction of benzylmagnesium chloride with 2-cyclohexenone (in presence of cuprous chloride)     

Effect of background derivatization on the signal enhancement of pesticide residues extracted from edible oils

The effect of background derivatization on the signal enhancement of pesticide residues extracted from edible oil samples was studied by GC with negative chemical ionization MS. The analytes were extracted by a solvent extraction process, and the extract was subjected to rapid low‐temperature fat precipitation. The residual fatty acids were silylated by derivatization with N,O‐bis(trimethylsilyl)trifluoroacetamide. The chromatograms obtained from the derivatized samples showed higher signal intensity and lower detection levels when compared to the direct analysis without derivatization. The sensitivity levels of the method are either better or comparable to that of previously reported methodologies. The LODs of the analyzed organochlorine, organophosphorus, and synthetic pyrethroid residues in sunflower, rice bran, and ground oil samples were in the range of 0.02–0.5 ng/g, and the LOQs were in the range of 0.1–2 ng/g. The intraday and interday accuracies were in the range of 81–116% with RSDs less than 14%. The recoveries obtained were in the range of 53–89% with the RSD values less than 13% for all the studied pesticide residues.     

Light meson spectrum and their leptonic decay widths in the frame work of constituent quark models

The phenomenological non-relativistic quark model has been employed to obtain the ground state masses of light vector mesons and their radially excited states and their decay widths.The full hamiltonian used in the investigation has kinetic energy,the confinement potential and the one-gluon-exchange potential.A good agreement is obtained with the experimental masses and their leptonic decay widths.     

LC‐MS/MS determination and pharmacokinetic study of lacidipine in human plasma

A robust, specific and fully validated LC‐MS/MS method as per general practices of industry has been developed for estimation of lacidipine (LAC) with 100 μL of human plasma using lacidipine‐¹³C8 as an internal standard (IS). The API‐4000 LC‐MS/MS was operated under the multiple reaction‐monitoring mode. A simple liquid–liquid extraction process was used to extract LAC and IS from human plasma. The total run time was 3.0 min and the elution of LAC and IS occurred at 1.96 and 1.97 min; this was achieved with a mobile phase consisting of 5 mm ammonium acetate buffer–acetontrile (15:85 v/v) at a flow rate of 0.60 mL/min on a Zorbax SB C₁₈ (50 × 4.6 mm, 5 µm) column. A linear response function was established for the range of concentrations 50–15,000 pg/mL (r > 0.998) for LAC. The current developed method has negligible matrix effect and is free from unwanted adducts and clusters which are formed owing to system such as solvent or mobile phase. The developed assay method was applied to an oral pharmacokinetic study in humans and successfully characterized the pharmacokinetic data up to 72 h. Copyright © 2013 John Wiley & Sons, Ltd.