Determination of diethylcarbamazine, an antifilarial drug, in human urine by H-1-NMR spectroscopy

被引:6
作者
Jaroszewski, JW [1 ]
Berenstein, D [1 ]
Slok, FA [1 ]
Simonsen, PE [1 ]
Agger, MK [1 ]
机构
[1] DANISH BILHARZIASIS LAB,DK-2920 CHARLOTTENLUND,DENMARK
关键词
DEC; quantitative H-1-NMR; solvent suppression; 1(3)over-bar3(1)over-bar pulse; urine analysis; drug excretion; drug metabolism; diethylcarbamazine N-oxide;
D O I
10.1016/0731-7085(95)01664-3
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
H-1-NMR spectroscopy is a convenient method for determination of diethylcarbamazine (DEC) in urine, and can be used to monitor medication with the drug. Urine samples were mixed with 10%, of deuterium oxide as a spectrometer field frequency lock, which is the only sample pretreatment required. Tailored excitation with the 1 (3) over bar 3 (1) over bar pulse was used for water peak suppression. The quantification of DEC was carried out with the triplet of the N-ethyl group, for which the T-1 relaxation rime was 1 s. In aqueous solutions, amounts below 1 mu g ml(-1) of DEC could be easily detected. In urine, the detectability depended on the level of chemical noise but was better than 10 mu g ml(-1). The accuracy and precision of the method were better than 15%. Analysis of urine from volunteers receiving a single therapeutic dose of DEC (6 mg kg(-1) body weight orally) showed that the drug was eliminated in unchanged form during 2 days, in agreement with earlier results. The concentration of DEC in urine several hours after the intake exceeded 100 mu g ml(-1) making the H-1-NMR assay rapid and easy. No significant amounts of the N-oxide of DEC could be detected.
引用
收藏
页码:543 / 549
页数:7
相关论文
共 30 条
[11]   DEALKYLATION AND N-OXIDATION IN METABOLISM OF I-DIETHYLCARBAMYL-4-METHYLPIPERAZINE IN RAT [J].
FAULKNER, JK ;
SMITH, KJA .
XENOBIOTICA, 1972, 2 (01) :59-&
[12]   ANALYSIS OF BIOLOGICAL-FLUIDS USING 600 MHZ PROTON NMR-SPECTROSCOPY - APPLICATION OF HOMONUCLEAR 2-DIMENSIONAL J-RESOLVED SPECTROSCOPY TO URINE AND BLOOD-PLASMA FOR SPECTRAL SIMPLIFICATION AND ASSIGNMENT [J].
FOXALL, PJD ;
PARKINSON, JA ;
SADLER, IH ;
LINDON, JC ;
NICHOLSON, JK .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 1993, 11 (01) :21-31
[13]  
GAYRAL P, 1989, ARZNEIMITTELFORSCH, V39-1, P226
[14]   SOLVENT SUPPRESSION IN FOURIER-TRANSFORM NUCLEAR MAGNETIC-RESONANCE [J].
HORE, PJ .
JOURNAL OF MAGNETIC RESONANCE, 1983, 55 (02) :283-300
[15]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ANALYSIS OF BASIC DRUGS ON SILICA COLUMNS USING NON-AQUEOUS IONIC ELUENTS .2. APPLICATION OF UV, FLUORESCENCE AND ELECTROCHEMICAL OXIDATION DETECTION [J].
JANE, I ;
MCKINNON, A ;
FLANAGAN, RJ .
JOURNAL OF CHROMATOGRAPHY, 1985, 323 (02) :191-225
[16]   A POSSIBLE CYTOCHROME-P-450-MEDIATED N-OXIDATION OF DIETHYLCARBAMAZINE [J].
JOSEPH, CA ;
DIXON, PAF .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1984, 36 (10) :711-712
[17]  
JOSEPH CA, 1984, J PHARM PHARMACOL, V36, P712
[18]   EXPERIMENTAL FILARIASIS OF DIPETALONEMA-DESSETAE IN PROECHIMYS-ORIS .3. EFFECTS OF PARASITISM ON THE PHARMACOKINETICS OF DIETHYLCARBAMAZINE [J].
KANI, F ;
GAYRAL, P ;
PFAFFDESSALES, MC ;
MAHUZIER, G ;
JACQUOT, C ;
AUGET, JL .
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 1983, 8 (04) :313-320
[19]  
KIMURA E, 1984, Southeast Asian Journal of Tropical Medicine and Public Health, V15, P74
[20]  
MORRE HG, 1950, Patent No. 495129