Comparison of LC-MS Assay and HPLC Assay of Busulfan in Clinical Pharmacokinetics Studies

Abstract

<jats:p>Busulfan is used in preparative regimens for bone marrow transplantation and timely busulfan plasma concentration reporting is critical for subsequent dose adjustment. We compared two sensitive methods for pharmacokinetics studies including LC-MS assay and HPLC precolumn derivatization assay. Chromatographic separation was performed on a Gemini C<jats:sub>18</jats:sub>column. Liquid-liquid extraction with ethyl acetate was used for plasma sample preparation. Busulfan and internal standard ([<jats:sup>2</jats:sup>H<jats:sub>8</jats:sub>]-busulfan) were detected as ammonium adducts at m/z 264.2 and 272.2 for LC-MS assay. For HPLC assay, the extraction from plasma was derivatized with 2-naphathalenethiol using synthesized internal standard (1,6-(methanesulfonyloxy)octane). The Ex and Em wavelength was 255 nm and 370 nm. The limit of detection was 15.6 ng/mL and 7.8 ng/mL for HPLC and LC-MS assay and good linearity ranging from 31.25–1000 ng/mL for HPLC and 15.6-1000 ng/mL for LC-MS assay. The intra and interday assay precision were less than 9.2% and 12.0% for LC-MS and HPLC assay. The pharmacokinetic parameters were estimated using noncompartmental pharmacokinetic model with WinNonlin. Busulfan AUClast showed an average difference of 0.7% between the two methods. The LC-MS method is accurate, reproducible, and requires less specimen, sample preparation and analysis time over the HPLC assay, making busulfan monitoring faster and easier in clinical practice.</jats:p>

Collagen: quantification, biomechanics and role of minor subtypes in cartilage

“…Another technique, using selected ion monitoring rather than MRM, foregoes ion pairing by using a silica hydride column; this method quantified HP and LP in skin and urine samples 90 . LC-MS is more sensitive and accurate than HPLC-FLD for several compounds [91][92][93] , although a thorough comparison between LC-MS and HPLC-FLD for collagen crosslink quantification has not been performed.…”

Raman spectroscopy as a potential tool for label free therapeutic drug monitoring in human serum: the case of busulfan and methotrexate

“…This Raman spectral response was validated to be linear over the entire range of 0.0003mg/mL to 0.0125mg/mL, which has not been fully validated in previous studies. In comparison to the earlier studies based on LC-MS, the present method shows similar performances in precision and recovery (13,16,24,56). However, In contrast, the proposed method with inverted Raman spectroscopy is cost-effective and easy to use, that can be translated as a point-of-care diagnostic tool for high-dosage MTX in bodily fluids.…”