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Biomedical subjects

Michelle Young

Publications and source records attributed to Michelle Young.

5 recordsLinked to original sources
PubMed2007

Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/tandem mass spectrometry.

Two fast and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based bioanalytical assays were developed and validated to quantify the active and three inactive metabolites of prasugrel. Prasugrel is a novel thienopyridine prodrug that is metabolized to the pharmacologically active metabolite in addition to three inactive metabolites, which directly relate to the formation and elimination of the active metabolite. After extraction and separation, the analytes were detected and quantified using a triple quadrupole mass spectrometer using positive electrospray ionization. The validated concentration range for the inactive metabolites assay was from 1 to 500 ng/mL for each of the three analytes. Additionally, a 5x dilution factor was validated. The interday accuracy ranged from -10.5% to 12.5% and the precision ranged from 2.4% to 6.6% for all three analytes. All results showed accuracy and precision within +/-20% at the lower limit of quantification and +/-15% at other levels. The validated concentration range for the active metabolite assay was from 0.5 to 250 ng/mL. Additionally, a 10x dilution factor was validated. The interbatch accuracy ranged from -7.00% to 5.98%, while the precision ranged from 0.98% to 3.39%. Derivatization of the active metabolite in blood with 2-bromo-3'-methoxyacetophenone immediately after collection was essential to ensure the stability of the metabolite during sample processing and storage. These methods have been applied to determine the concentrations of the active and inactive metabolites of prasugrel in human plasma.

Chromatography, High Pressure Liquid↗
PubMed2006

Identification of aberrant 2'-5' RNA linkage isomers by pellicular anion exchange chromatography.

During chemical RNA synthesis, many undesired products may be formed. In addition to the "n-x" sequences, depurination products, and incompletely deprotected oligonucleotides, linkage isomers may form during condensation and/or deprotection of the synthetic products. Under acidic conditions, bond migration may alter normal 3'-5' diesters to aberrant 2'-5' diesters. This results in isomers that are difficult to identify by MS and LC-MS techniques because the isomers have identical masses. HPLC methods for identification of these isomers have not advanced because the isomers are not expected to exhibit differences in hydrophobicity that allow resolution by reversed-phase columns. Neither are changes in ionic interactions anticipated for these isomers that would allow resolution by ion exchange methods. We observed that chromatography on pellicular anion exchange phases, but not on porous anion exchange phases, completely resolves oligonucleotides with very slight conformation differences (e.g., DNA vs. RNA of identical sequence). Because incorporation of 2'-5' linkages in RNA will alter solution conformation slightly, we considered that this pellicular ion exchanger might also allow resolution of identical RNA sequences harboring aberrant 2'-5' linkages from those lacking aberrant 2'-5' linkages. Using the nonporous DNAPac PA200 column, we demonstrated a chromatographic procedure for resolving synthetic RNA with aberrant linkages from their normally linked counterparts. Under certain conditions, aberrant isomers are not completely resolved from those containing only normal linkages. Therefore, we also developed an independent linkage-confirming method using a 5'-3' exonuclease. This enzyme produces incomplete digestion products during digestion of synthetic RNA containing aberrant 2'-5' linkages, and these are readily resolved by DNAPac PA200 chromatography.

Chromatography, High Pressure Liquid↗
PubMed2003

Successful pregnancy outcome following 19 consecutive miscarriages: case report.

No cause can be found in 50% of patients with recurrent miscarriage. Recent research has shown that high levels of natural killer (NK) cells within the endometrium may be associated with idiopathic recurrent miscarriage. This case report describes a patient in whom an excessive number of uterine NK cells were found. She received preconceptual prednisolone and delivered a live baby. This is a novel observation of untested significance.

Abortion, Habitual↗