Determination of linsidomine in human plasma by tandem LC–MS with ESI

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 22; no. 3; pp. 461 - 467
• Main Authors: Sutherland, F.C.W, de Jager, A.D, Swart, K.J, Hundt, H.K.L, Scanes, T, Hundt, A.F
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01-04-2000; Elsevier Science
• Subjects: Analysis; Biological and medical sciences; Chromatography, Liquid - methods; Electrospray; General pharmacology; Humans; Ion Exchange; Linsidomine; Liquid chromatography; Mass spectrometry; Mass Spectrometry - methods; Medical sciences; Molsidomine - analogs & derivatives; Molsidomine - blood; Pharmacology. Drug treatments; Plasma; Quality Control; Reproducibility of Results; Vasodilator Agents - blood; Linsidomine; Plasma; Liquid chromatography; Mass spectrometry; Electrospray; Antianginal agent; Biological fluid; Coronary vasodilator agent; Spraying; HPLC chromatography; In vitro; Blood plasma; Electric field; Mass spectrometry MS/MS; Separation process; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(00)00239-9

A sensitive method for the determination of linsidomine in plasma was developed, using high-performance liquid chromatographic (HPLC) separation with tandem mass spectrometric detection. Linsidomine was derivatised with propyl chloroformate and extracted with
tert-butyl methyl ether/1,2-dichloroethane (55:45, v/v), back-extracted into HCl (0.01 M) followed by alkalinisation and back-extraction into ether; the final ether extract evaporated, reconstituted in mobile phase and then separated on a Phenomenex® Luna C18 (2) 5 μ 2.1×150 mm column with a mobile phase consisting of methanol–water–formic acid (98/100%) (400:600:0.05, v/v/v) at a flow-rate of 0.4 ml min
−1. Detection was achieved by a Finnigan MAT mass spectrometer (LCQ) at unit resolution in the selected reaction monitoring (SRM) mode monitoring the transition of the protonated molecular ion
m/
z 257.0 to the product ion
m/
z 86.0. The mean recovery for linsidomine was 51% with a lower limit of quantification of 0.70 ng/ml using 1 ml plasma for extraction. This LC–MS/MS method for the determination of linsidomine in human plasma allows for better specificity and a higher sample throughput than the traditional LC–UV methods. It also demonstrates the profound effect that the composition of acidic modifiers and matrix constituents can have on the electrospray ionisation (ESI) of the analyte.