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Analysis of lanthionine ketimine ethyl ester in mouse serum, whole blood and tissues using ultrahigh-pressure liquid chromatography/tandem mass spectrometry.
Muchiri, Ruth N; Kowal, Katarzyna E; Hensley, Kenneth; Feinstein, Douglas L; van Breemen, Richard B.
Afiliação
  • Muchiri RN; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
  • Kowal KE; Department of Veterans Affairs, Jesse Brown VA Medical Center, University of Illinois at Chicago, IL, USA.
  • Hensley K; Arkansas College of Osteopathic Medicine, Fort Smith, AR, USA.
  • Feinstein DL; Department of Veterans Affairs, Jesse Brown VA Medical Center, University of Illinois at Chicago, IL, USA.
  • van Breemen RB; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
Rapid Commun Mass Spectrom ; 32(22): 1941-1948, 2018 Nov 30.
Article em En | MEDLINE | ID: mdl-30117207
ABSTRACT
RATIONALE Preclinical studies in the search for treatments for several neurodegenerative diseases have identified lanthionine ketimine (LK) and its monoethyl ester derivative (LKE) as potential candidates. An ultrahigh-pressure liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) assay was developed to evaluate bioavailability by measuring these compounds in mouse serum, whole blood and brain tissue.

METHODS:

Following administration of LKE to mice for 3 days in chow at 300 ppm, the animals were sacrificed, and LKE was extracted from serum, whole blood and brain tissues through protein precipitation using cold methanol. To enhance chromatographic separation and electrospray ionization, LK was methylated using diazomethane. Separations were carried out using C18 reversed-phase UHPLC, and quantitative measurements were obtained using on-line triple-quadruple mass spectrometry with positive ion electrospray ionization, collision-induced dissociation and selected reaction monitoring. Tolbutamide was used as internal standard.

RESULTS:

LKE showed good recovery ranging from 77-90% in serum and 82-88% in brain tissue. An eight-point standard curve ranging from 0.005 to 4.6 µM was linear (R2 0.998). The average LKE detected in mouse serum was 277.42 nM, while the concentration in whole blood was 38 nM. Neither LK nor LKE was detected in brain tissues.

CONCLUSIONS:

A rapid quantitative method to measure LKE in mouse serum, whole blood and brain tissues using UHPLC/MS/MS was developed and validated following FDA guidelines. This method is suitable for bioavailability and pharmacokinetic studies.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Espectrometria de Massas em Tandem / Aminoácidos Sulfúricos Tipo de estudo: Guideline Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Espectrometria de Massas em Tandem / Aminoácidos Sulfúricos Tipo de estudo: Guideline Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article