Validation of a Low-Volume Plasma LC-MS/MS Method Using a Capillary Microsampling (CMS) Technique
In recent years there has been much discussion related to the use of fewer animals for pre-clinical safety and efficacy testing. In addition, regulatory agencies have requested testing in pediatric patient populations for all new drug compounds. With the development of more sensitive instrumentation, the need for smaller blood sample size analysis, has been realized. Over the years, techniques such as Dried Blood Spot (DBS) have been utilized to sample less than 50 uL of blood. While DBS seems to work well for many analyses, the historical PK database for most clinical trials has been through the quantitation of drugs from plasma or serum.
Quantitation of Four Chiral Drug Compounds Simultaneously Using Normal Phase LC-MS/MS Equipped With an APPI Ion Source
Chiral separation is important but also challenging in bioanalytical plasma analysis. The investigation of luliconazole efficacy requires the measurement of its two geometric isomers (E/Z or trans/cis forms), as well as their chiral (R and S) forms. To measure the individual concentrations of the four chiral compounds by LC-MS/MS, it is necessary to chromatographically separate all four enantiomers. As expected, baseline separation was only achieved between E and Z forms with non-chiral columns. With chiral columns, good separation was achieved between RE and SE, or RZ and SZ, separately, but not all of the chiral compounds.
Determination of Fluticasone Propionate and Fluticasone 17&[beta]-Carboxylic Acid Propionate (Fluticasone Metabolite) in Human Plasma by LC-MS/MS
In this study, we developed and validated a LC-MS/MS method for the determination of Fluticasone propionate and Fluticasone 17β-carboxylic acid propionate (Fluticasone metabolite) in human K3EDTA plasma using Fluticasone propionate-d5 and Fluticasone 17β-carboxylic acid propionate-d3 as the internal standards (IS) using positive and negative TIS switch during analysis
Comparison of the Quantitative Measurement of Albumin in Human Plasma Using ELISA and uHPLC-High Resolution Mass Spectrometry
Human serum albumin (HSA) is the most abundant protein in human blood plasma. It is comprised of 585 residues with 17 disulfide bonds. Cys34 is its single free thiol group which is thought to act as an oxidant scavenger. Previous chromatographic studies have shown that the HSA-SH fraction of HSA decreases with age; 76% vs. 48%, young vs elderly healthy male subjects, respectively.1,2 The lower percent of SH present is a measure of the frailty of the person. Since ELISA can only measure total albumin, it does not provide a complete assessment of the person’s overall health. Although typical serum albumin levels range from 35-50 mg/mL of serum, lower or higher levels of certain serum albumins indicate disease states (e.g., Cirrhosis of the liver, severe dehydration-kidney disease) which requires treatment. Thus test kits that simply measure the total amount of HSA present in blood plasma may not completely describe the patient condition regarding a measure of frailty of the patient. This poster presents the ability of using LC coupled to high resolution mass spectrometry (HRMS) for the analysis of the different intact albumin proteins.
Development and Validation of an Ultra Sensitive LC-MS/MS Method for Quantitation of Midazolam in Human Plasma
Midazolam is a widely used central nervous system depressant. It is used for the treatment of insomnia, seizure, and induction of sedation or amnesia for operations. Midazolam is metabolized by cytochrome CYP3A. It is a widely used probing drug for evaluation of CYP3A activity in drug-to-drug interaction (DDI) studies.
Determination of Pregabalin in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry
Pregabalin, (S)-3-(aminomethyl)-5-methylhexanoic acid, is an analogue of the neurotransmitter gamma amino butyric acid (GABA). It is used for the treatment of peripheral and central neuropathic pain in adults and as an adjunctive therapy for refractory partial seizures. Pregabalin binds potently to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system and its binding at this site reduces calcium influx at the nerve terminal, leading to the release of several neurotransmitters, such as glutamate and noradrenalin. The aim of this study is to develop a sensitive, specific, robust and rapid LC-MS/MS method: Use simple extraction procedure; With no interference from matrix; With short run time.
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