Minsoo Kim
Chung-Ang University, South Korea
Title: Quantitative determination of sulfisoxazole and its three N-acetylatedmetabolites using HPLC–MS/MS, and the saturable pharmacokineticsof sulfisoxazole in mice
Biography
Biography: Minsoo Kim
Abstract
Sulfisoxazole (SFX) is still used in combination with trimethoprim in cattle despite adverse drug reactions(e.g., urolithiasis). Recently, SFX is known to be a promising repositioned drug candidate for pulmonaryhypertension and cancer. We developed a simultaneous determination method of SFX and its N-acetylated metabolites (N1-acetyl SFX, N1AS; N4-acetyl SFX, N4AS; diacetyl SFX, DAS) using HPLC–MS/MSfor the first time, and examined the pharmacokinetics of SFX in mice. N1AS and DAS were convertedrapidly to SFX and N4AS, respectively, in mouse plasma. The time courses of plasma SFX and N4AS con-centrations were well-characterised following the oral administration of SFX to mice. The absorption,metabolism, and/or excretion of SFX given at >700 mg/kg may be saturable, and in contrast to humansand rats, the extent of systemic exposure of mice to N4AS was much greater than that of SFX. Interestingly,the acetyl groups at both N1- and N4-positions were degraded during the ionisation required to generateprecursor ions. In additional experiments the carboxyl group of N-acetyl-5-aminosalicylic acid(NA5AS)was lost instead of the acetyl group during the ionisation, and acetaminophen (AAP) appeared. As theacetyl and carboxyl groups of some substances can be degraded during ionisation in the mass spectrom-eter, caution is appropriate when it is sought to simultaneously quantify similar structures containingthese moieties; chromatographic separation is essential.