Determination of the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl) piperazine (IP/66) in rat and human plasma by high-performance liquid chromatography and isotope dilution mass spectrometry.
In connection with pharmacokinetic studies on the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine (IP/66) (I), appropriate high-performance liquid chromatographic (HPLC) and gas chromatographic-mass spectrometric isotope dilution (GC-MS-ID) methods for its determination in rat and human plasma, respectively, were developed. In both techniques, deproteinized and basified plasma samples were extracted and purified by adsorption on an Extrelut-1 column, then the drug was eluted with dichloromethane. Quantitative HPLC analysis was performed on a C8 reversed-phase column. The mobile phase was phosphate buffer (0.02 M, pH 2.8)-acetonitrile (65:35), with UV detection at 208 nm. The internal standard was 1-[2-butoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine, a homologue of I. The inter-assay coefficient of variation (C.V.) was 9.9% for a drug level of 2 micrograms/ml. Quantitative GC-MS-ID analysis was performed with a DB-17 fused-silica capillary column using the selected-ion monitoring technique. The deuterated form of I, 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-2'-trideuteromethoxyphenyl)pipe razine, utilized as internal standard, was synthesized. The inter-assay C.V. was 7.36% for a drug level of 1 ng/ml.
Agostini
O
O
Research Laboratories, Analytical Department, Istituto Farmacobiologico MALESCI SpA, Florence, Italy.
Moneti
G
G
Bonacchi
G
G
Fedi
M
M
Manzini
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010879:Piperazines / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D013607:Tablets
D000959:Antihypertensive Agents; D010879:Piperazines; D013607:Tablets; C040940:IP 66