TY - JOUR
T1 - Gas chromatographic determination of novel valproyl taurinamide derivatives in mouse and dog plasma
AU - Isoherranen, Nina
AU - Yagen, Boris
AU - Spiegelstein, Ofer
AU - Steinman, Amir
AU - Finnell, Richard H.
AU - Bialer, Meir
N1 - Funding Information:
This study was supported in part by the Horowitz fund of the Hebrew University of Jerusalem, Israel.
PY - 2003/5/5
Y1 - 2003/5/5
N2 - Valproyl taurinamides are a novel group of compounds that possess anticonvulsant activity. In this study a gas chromatographic micromethod was developed for the quantification of selected valproyl taurinamides and some of their metabolites in biological samples. Valproyl taurinamide (VTD), N-methyl valproyl taurinamide (M-VTD), N,N-dimethyl valproyl taurinamide (DM-VTD) and N-isopropyl valproyl taurinamide (I-VTD) were analyzed in mouse and dog plasma and in dog urine using gas chromatography. Flame ionization detection and mass spectrometric detection were compared. The plasma samples were prepared by solid-phase extraction using C18 cartridges. The urine samples were prepared by liquid-liquid extraction. The sample volume used was 100 μl of dog plasma, 50 μl of mouse plasma and 20 μl of dog or mouse urine. The quantification range of the method was 1.5-50 mg/l in dog plasma (VTD only), 2.5-250 mg/l in mouse plasma (0.7-90 pmol injected) and 0.04-2 mg/ml in dog urine (VTD only). The inter-day precision in plasma and urine samples was around 10% for all quantified concentrations except LOQ (15-20%). The accuracy for all four compounds was between 90 and 110% within the entire concentration range. The developed method was suitable for quantification of a series of CNS-active valproyl taurineamide derivatives in biological samples at relevant in vivo concentrations.
AB - Valproyl taurinamides are a novel group of compounds that possess anticonvulsant activity. In this study a gas chromatographic micromethod was developed for the quantification of selected valproyl taurinamides and some of their metabolites in biological samples. Valproyl taurinamide (VTD), N-methyl valproyl taurinamide (M-VTD), N,N-dimethyl valproyl taurinamide (DM-VTD) and N-isopropyl valproyl taurinamide (I-VTD) were analyzed in mouse and dog plasma and in dog urine using gas chromatography. Flame ionization detection and mass spectrometric detection were compared. The plasma samples were prepared by solid-phase extraction using C18 cartridges. The urine samples were prepared by liquid-liquid extraction. The sample volume used was 100 μl of dog plasma, 50 μl of mouse plasma and 20 μl of dog or mouse urine. The quantification range of the method was 1.5-50 mg/l in dog plasma (VTD only), 2.5-250 mg/l in mouse plasma (0.7-90 pmol injected) and 0.04-2 mg/ml in dog urine (VTD only). The inter-day precision in plasma and urine samples was around 10% for all quantified concentrations except LOQ (15-20%). The accuracy for all four compounds was between 90 and 110% within the entire concentration range. The developed method was suitable for quantification of a series of CNS-active valproyl taurineamide derivatives in biological samples at relevant in vivo concentrations.
KW - Derivatization, GC
KW - Valproyl taurinamide
UR - http://www.scopus.com/inward/record.url?scp=0037420714&partnerID=8YFLogxK
U2 - 10.1016/S1570-0232(02)01034-6
DO - 10.1016/S1570-0232(02)01034-6
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C2 - 12668078
AN - SCOPUS:0037420714
SN - 1570-0232
VL - 788
SP - 125
EP - 136
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 1
ER -