Interference from a glucuronide metabolite in the determination of ramipril and ramiprilat in human plasma and urine by gas chromatography-mass spectrometry.
J Pharm Biomed Anal
; 40(3): 794-8, 2006 Feb 24.
Article
em En
| MEDLINE
| ID: mdl-16242284
ABSTRACT
In the course of development and validation of a gas chromatography-mass spectrometry (GC-MS) method for ramipril and its biologically active metabolite ramiprilat, evidence was found for an unknown interfering metabolite. Sample treatment included isolation from plasma or urine by solid-phase extraction, methylation with trimethylsilyldiazomethane and acylation with trifluoroacetic anhydride (TFAA). When liquid chromatography was used to fractionate plasma extracts prior to derivatization, the alkyl, acyl-derivative of ramipril was obtained from two separate LC fractions. Electrospray ionization mass spectral data, together with circumstances for the derivatization, were consistent with the presence of an N-glucuronide of ramipril. Interference from the metabolite was eliminated by including a wash step after extraction/alkylation, prior to acylation. The final assay had a lower limit of quantification at 1.0 nmol/L and a linear range of 1-300 nmol/L. Intra- and inter-batch precision for ramipril and ramiprilat in plasma or urine were better than 10 and 5% at 2 and 80 nmol/L, respectively.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores da Enzima Conversora de Angiotensina
/
Ramipril
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article