High-Performance liquid chromatographic determination of dibromomannitol in plasma

Abstract

Myelobromol 1,6-dibromo-l,6-dideoxy-D-mannitol (dibromomannitol, DBM) is a bifunctional alkylating agent that has been in clinical use since 1963. It is currently included at high dose in preconditioning regimen for bone marrow transplantation (BMT) and is a mainstay of treatment for polycythaemia vera. A highperformance liquid chromatographic method was developed for the determination of DBM in the plasma. The bhsis of the assay is a derivatization with sodiumdiethyldithiocarbamate at 42 ~ in the presence of 1bromo-l-deoxy-3,6-anhydro-galactitol as internal standard (IS). The analysis was carried out on a 250 • 4 mm Hypersil 5 CPS column equipped with a 20 • 4 mm Hypersil 10 CPS precolumn. The eluent consisted of heptane:isopropyl-alcohol:glacial acetic acid = 600:76:80 w/w. The flow rate was 1.2 mL rain -1. UV detection was performed at 254 rim. The calibration graph was linear in the concentration range of 2.5-260/aM of DBM in plasma. The limit of detection was 1.0 pM. The precision and accuracy of the method was between the good laboratory practice (GLP) required limits.

High-performance liquid chromatographic determination of busulfan in plasma

“…DDTC was selected, because it has been widely used for derivatization of anticancer alkylating agents [18][19][20][21][22][23][24][25][26]. BU reacts in aqueous solution with DDTC.…”

“…Analogous compounds such as 1,6-bis-(methanesulfonyloxy)hexane [20,21 ] [27] suitable as an IS are not available as commercial products. Our choice was BAD, a monofunctional alkylating compound, available as a crystalline and stable material, which is, in similar circumstances, routinely used as an IS for the determination of a bifunctional anticancer alkylating agent, dibromomannitol (DBM, myelobromol) [26]. Spectra of derivatized BU and BAD were very similar, with absorbance maxima at 252 and 280 nm and absorbance minima at 235 and 261 nm (Figures la, b).…”