WITHDRAWN: Quality by design (QbD) approach to analytical RP-HPLC method development and its validation of Etophylline & Theophylline.

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A Review on the Current Principles of Antibiotic Therapy for Diabetic Foot Infection.

Foot infections, being one of the major complications, account for nearly 15% of people with diabetes, and increase their risk for amputation in lower extremities. Though various factors contribute to the development of diabetic foot infection, poor glycemic control poses a greater risk paving the way for a number of micro-organisms to colonize the wound. In order to restore the lost granulation tissue at the ulcer site, the prime aim should not only be attaining glycemic control but also must focus on performing culture by clinically differentiating the stage of infection as well as to manage or control the infection by selecting a rational empiric antibiotic regimen, amidst the uncertainty that exists in choosing best antimicrobial therapy in emerging multi-drug resistance worldwide. This review mainly analyzes that although among the existence of various undefined microbiome being prevalent in causing diabetic foot infections, how the current trend of antibiotics in use aids in treating foot infections in diabetes.

Enhancement of drug permeability across blood brain barrier using nanoparticles in meningitis.

The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier regulating its homeostasis. Blood-brain barrier is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the blood-brain barrier also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the blood-brain barrier. Within this review a brief description of the structural and physiological features of the barriers and the recently born strategy of brain drug delivery based on the use of nanoparticles are described. Finally, the future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments.

Highly Sensitive LC-MS-MS Method for the Determination of Tacrine in Rat Plasma: Application to Pharmacokinetic Studies in Rats.

A rapid and highly sensitive assay method has been developed and validated for the estimation of tacrine in rat plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves a simple liquid-liquid extraction of tacrine and phenacetin (internal standard, IS) from rat plasma using ethyl acetate. Chromatographic separation was achieved with 0.2% formic acid : acetonitrile (30 : 70, v/v) at a flow rate of 0.50 mL/min on an Atlantis dC18 column with a total run time of 3.0 min. The MS-MS ion transitions monitored were 199.10 → 171.20 for tacrine and 180.10 → 110.10 for IS. Method validation was performed as per United States Food and Drug Administration (US FDA) guidelines and the results met the acceptance criteria. The lower limit of quantification achieved was 0.008 ng/mL and linearity was observed from 0.008 to 53.4 ng/mL. The intra- and inter-day precision was in the range of 2.76-12.5 and 5.15-12.8%, respectively. This novel method has been applied to a pharmacokinetic study in rats.

Highly sensitive LC-MS/MS method for determination of galantamine in rat plasma: application to pharmacokinetic studies in rats.

A rapid and highly sensitive assay method has been developed and validated for the estimation of galantamine (GLM) in rat plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves a simple liquid-liquid extraction of GLM and phenacetin (internal standard, IS) from rat plasma using acetonitrile. Chromatographic separation was achieved with 0.2% formic acid:acetonitrile (50:50, v/v) at a flow rate of 0.60 mL/min on an Atlantis dC18 column with a total run time 2.5 min. The MS/MS ion transitions monitored were 288.10 → 213.10 for GLM and 180.10 → 110.10 for IS. Method validation was performed as per United States Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.12 ng/mL and linearity was observed from 0.12 to 525 ng/mL. The intra- and inter-day precision were in the ranges of 4.73-11.7 and 5.83-8.64%, respectively. This novel method has been applied to a pharmacokinetic study in rats.

Review of the validated HPLC and LC-MS/MS methods for determination of drugs used in clinical practice for Alzheimer's disease.

Alzheimer's disease (AD) is a neurological disorder and is the most frequent type of dementia among elderly people. Donepezil, rivastigmine, galantamine, tacrine and memantine are the US Food and Drug Administration approved oral drugs used in the treatment of AD. Quantitation of these drugs in various biological matrices and monitoring them in long-term treatment is essential to titer the dose of these drugs and ensure patient compliance. This review provides a comprehensive account of various HPLC and LC-MS/MS assays, which have been successfully employed to measure the drug levels in various biological matrices arising from preclinical and clinical studies. In addition, this review collates various considerations such as internal standard selection, extraction schemes, matrix effect, selectivity evaluation and optimization of mass spectrometric conditions to enable the development of sound bioanalytical methods for quantitation of Alzheimer's drugs. Overall LC-MS/MS methods have proven to be the choice of bioanalytical method for the quantification of Alzheimer's drugs in both preclinical and clinical studies. In conclusion, important features of LC-MS/MS methodology for Alzheimer's drugs include shortened analysis time, increased throughput, selectivity and lower cost of analysis.