title: A novel extraction method based on a reversible chemical conversion for the LC/MS/MS analysis of the stable organic germanium compound Ge-132.
abstract: Poly trans-[(2-carboxyethyl)germasesquioxane] (IUPAC name) is the most common water-soluble organic germanium compound. This compound is known as bis(carboxyethyl)germaniumsesquioxide and it is commonly called Ge-132; it is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGPA) in water. We have developed a method for the quantification of THGPA in rat plasma, using a novel extraction method based on a reversible chemical conversion. THGPA in plasma is converted to 3-(trichlorogermyl)propanoic acid (TCGPA) under acidic conditions using concentrated hydrochloride, which is followed by extraction with chloroform. TCGPA is then converted back to THGPA through hydrolysis. The extraction recovery of this method is approximately 100%. Moreover, we synthesized deuterated Ge-132, which was used as an internal standard in our experiments. This method covers a linearity range of 0.01-5 μg/mL for concentrations of THGPA in plasma. The intra-day and inter-day precisions of the analysis are about 4.1%, and the accuracy is within ±2.6% at THGPA concentrations of 0.025, 0.25, and 2.5 μg/mL. The total run time is 5 min. Our method was successfully applied to a pharmacokinetic investigation following oral administration of Ge-132.
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital , 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005857:Germanium; D006868:Hydrolysis; D057230:Limit of Detection; D008297:Male; D009942:Organometallic Compounds / Q000097:blood* / Q000737:chemistry; D011422:Propionates; D017208:Rats, Wistar; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C000601533:3-(trihydroxygermyl)propanoic acid; D009942:Organometallic Compounds; D011422:Propionates; D005857:Germanium; C066750:propagermanium