Determination of 1,3-di(4-imidazolino-2-methoxyphenoxy)propane in rat, dog and human plasma and urine by high-performance liquid chromatography with fluorescence detection.
A sensitive and selective high-performance liquid chromatographic (HPLC) method was developed for the determination of 1,3-di(4-imidazolino-2-methoxyphenoxy)propane (DMP) in rat, dog and human plasma (50-5000 ng/ml) and urine (0.1-10 micrograms/ml). DMP and DMPent (dimethoxyimidizolinopentamidine, the internal standard), are extracted from alkanized plasma with n-butyl chloride-n-butanol (9:1, v/v). The organic phase is dried under nitrogen, reconstituted in mobile phase, and washed with hexane. Separation is achieved by ion-pair chromatography on a Zorbax Rx C8 column with fluorescence detection. The analysis of pooled plasma (80, 400, and 4000 ng/ml) and urine controls (0.3, 1.6, and 8 micrograms/ml) demonstrated excellent precision and accuracy over a three-day period. The recovery of DMP is > 90% from rat, dog, and human plasma and > 85% from rat and human urine, and 60-70% from dog urine. The limit of quantitation (LOQ) of the assay is 50 ng/ml in rat, dog and human plasma. Using the high-sensitivity assay, the limit of quantitation was decreased to 5, 2 and 0.6 ng/ml in rat, dog and human plasma, respectively. The LOQ of the assay is 0.1 microgram/ml in rat, dog and human urine. The assay was used to determine plasma and urine concentrations of DMP in pharmacokinetic studies in rat and dog.
Hanson
G D
GD
Hazleton Wisconsin, Department of Biopharmaceutics, Madison 53704.
Slattum
P
P
Tidwell
R R
RR
Bekersky
I
I
Mong
S
S
D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006801:Humans; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D010419:Pentamidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000652:urine; D011786:Quality Control; D051381:Rats; D013050:Spectrometry, Fluorescence
D000981:Antiprotozoal Agents; D007202:Indicators and Reagents; C065259:1,3-di-(4-imidazolino-2-methoxyphenoxy)propane; D010419:Pentamidine