Hopantenic acid

CN (( )-4-[(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)amino]butanoic acid calcium salt (2 1) hopantenic acid... 

Ganno, K. (1997), Measuiemenl of pantothenic acid and hopantenic acid by gas chroma-lography-mas-s spectroscopy. Mefiwds EnzymeJ. 279, Part 1,213-219,... 

The pantothenic acid derivatives include pantothenic acid (BAN), pantothenol (BAN), dexpanthenol (rINN), and hopantenic acid (rINN). 

Banno, K., Matsuoka, M., Horimoto, S., and Kato, J., 1990. Simultaneous determination of pantothenic acid and hopantenic acid in biological samples and natural products by gas chromatography-mass fragmentography. Journal of Chromatography. 525 255-264. 

The natural higher homologue of pantothenic acid called homopantothenic or hopantenic acid (Fig. 7) occurs in biological fluids of animals (23,24). 

The calcium salt of hopantenic acid (Fig. 7) has been used for improving blood circulation and metabolism in the brain (26). 

The determination of trimethylsilylated pantoyllactone by gas chromatography-mass fragmentography (GC-MF) with a packed column has been developed for the assay of pantothenic acid by Tarli et al. (23). Umeno et al. (24) used the same method to investigate hopantenic acid levels in serum and urine after administration of calcium hopantenate. 

Simultaneous rapid microanalysis of pantothenic acid and hopantenic acid in biological samples (plasma and brain samples) and foodstuffs (rice, green tea, and dried yeasts) by GC-MF was recently described by Banno et al. (55). Plasma samples were purified without deproteinization on an ion exchange resin MCI GEL CK08P (170 X 10 mm, H+), and the eluate was extracted with ethyl acetate under acidic conditions. The organic layer was evaporated and the residue sily-lated with bis(trimethylsilyl)trifluoroacetamide. The brain samples were homoge-... 

Aliquots of this solution were analyzed by GC-MF using a wide-bore fiised-silica column (DB-T7, 15 m X 0.53 mm) with a flow rate of helium of 15 vaL min, and the injection port, column oven, and separator temperatures of 250°C, 200°C, and 250°C, respectively. The MS detector was operating in the electron impact mode at 70 eV, the ionization current was 100 pA and the temperature of the ion source was 200°C. The stable fragment ions [M-CHs] selected for multiple ion detection were at m/z 420,434, and 448. They were produced from the trimethylsilyl derivatives of pantothenic acid, hopantenic acid, and 5-[2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)amino]pentanoic acid (internal standard), respectively (Fig. 30). 

The calibration curves were linear in the range 5 to 100 ng/mL of plasma and the detection limits were ca. 1 ng/mL plasma samples. The average recoveries of pantothenic acid and hopantenic acid were 92.9 4.6% and 95.5 5.1%, respectively. 

Optical Isomers of Pantothenic Acid and Hopantenic Acid... 

GC-MF was also used for the chiral separation and simultaneous determination of pantothenic acid and hopantenic acid enantiomers in rat plasma (56). The method is based on derivatization of the acids and separation of the volatile products using a chiral stationary phase. 

The plasma samples were purified on an anion exchange resin MCI GEL CA08P (170 X 10 mm. Cl ). DL-Pantothenic acid and DL-hopantenic acid were eluted with 1 M NaCl solution and free acids were extracted with ethyl acetate from the eluate acidified with 6 M HCl in the presence of ammonium sulfate and esterified with 1.5 M HCl in methanol at room temperature for 1 h. The resulting methyl esters were trifluoroacetylated with trifluoroacetic anhydride in dichloro-methane at room temperature for 30 min and analyzed by GC-MF. Mass spectrometry with selected-ion monitoring was employed for the simultaneous determination of the enantiomers of pantothenic acid and hopanthenic acid. The stable mass fragments were detected at m/z 257 and 271, being the base peaks of pantothenic acid and hopantenic acid, respectively (Fig. 31). 

The calibration curves were linear in the 50 to 2000 ng/mL range. The recoveries of L-pantothenic acid and L-hopantenic acid were 93.5 5.5% and 92.4 8.3%, respectively. The detection limits of pantothenic acid and hopantenic acid were 5 ng/mL and 12 ng/mL, respectively. 

Figure 31 Mass fragmentogram of methyl bis(trifluoroacetates) of DL-pantothenic acid and DL-hopantenic acid. Column fused sihca capillary, 20 m X 0.22 mm, film thickness 0.12 fim stationary phase Chirasil-D-Val coated with L-valine-terr-hutylamide mobile phase helium, 1 kg/cm split ratio 1 30 temperatures injector 180°C, column 130°C, separator 250°C, ion source 250°C detector not specified ions miz 257, 271, and 285 peak identification (1) L-pantothenic acid (2) D-pantothenic acid (3) L-hopantenic acid (4) D-hopantenic acid (5) D-5-[2,4-dihydroxy-3,3-dimethyl-l-oxobutylamino]pentanoic acid (internal standard). (From Ref. 56.)...

Randomised studies In a randomised study to evaluate the efficacy and safety of hopantenic acid in children with cerebral palsy, there was no evidence of a serious effect on visual-motor skills. Hopantenic acid demonstrated a high safety profile [15 ]. 

LC-MS method to measure the concentration of vitamin B5 in human urine. Hopantenic acid (HOPA) is used as internal standard. Quantitative MS detection is performed in the single-ion monitoring mode. A linear calibration curve was obtained with F = 0.999 in the concentration range of 0.25-10 p-g/ml. The lower limit of detection is 0.1 pg/ml, with an intraassay coefficient of variation <5% and recoveries between 96 and 108%. 

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