Differential Stability of Various Analogs of Cobalamin to Vitamin C

Frost, Douglas V.; Lapidus, Milton; Plaut, Katharine Armstrong; Scherfling, Erna; Fricke, Howard H.

doi:10.1126/science.116.3005.119

Cited by 37 publications

(12 citation statements)

References 5 publications

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“…These changes were more rapid in the degraded solution of B 12b . The color changes involved in the degradation of B 12 have been ascribed to the formation of the reduced form of B 12 (B 12r ) (red to reddish brown), reaction intermediates (brown to yellow) and corrin ring oxidation products (yellow to colorless) (24). In the presence of air B 12r is slowly oxidized to B 12b (32): similar rapid color changes have been observed in B 12b solutions, degraded in the presence of AH 2 .…”

Section: Resultsmentioning

confidence: 57%

“…B 12b is very unstable in the presence of AH 2 and is destroyed by the release of Co atom with subsequent disappearance of the color (12,24,28,29). These changes result in the cleavage of the corrin ring to form the oxidation products (9,12,28).…”

Section: Mode Of Degradationmentioning

confidence: 99%

“…Similar reactions occur on the chemical degradation of B 12 and B 12b in the presence of ascorbic acid (AH 2 ) (12)(13)(14) and may be expressed as follows: The effect of thiamine (15,16), nicotinamide (17,18), and riboflavin (19)(20)(21)(22) on the photolysis of B 12 and B 12b has been investigated. Several studies have been conducted on the incompatibility and interaction of B 12 and AH 2 that lead to the loss of B 12 in aqueous solution (12,13,(23)(24)(25)(26)(27). B 12b has been found to be less stable than B 12 in the presence of AH 2 (28)(29)(30) and is destroyed to form unknown oxidation products ( 9 , 12,31, 32).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Ascorbic Acid on the Degradation of Cyanocobalamin and Hydroxocobalamin in Aqueous Solution: A Kinetic Study

et al. 2014

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Abstract. The degradation kinetics of 5×10−5 M cyanocobalamin (B 12 ) and hydroxocobalamin (B 12b ) in the presence of ascorbic acid (AH 2 ) was studied in the pH range of 1. , respectively, indicating a greater effect of AH 2 on B 12b compared to that of B 12 . The k obs -pH profiles for both B 12 and B 12b show the highest rates of degradation around pH 5. The degradation of B 12 and B 12b by AH 2 is affected by the catalytic effect of phosphate ions on the oxidation of AH 2 in the pH range 6.0-8.0.

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Section: Resultsmentioning

confidence: 57%

Section: Mode Of Degradationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Ascorbic Acid on the Degradation of Cyanocobalamin and Hydroxocobalamin in Aqueous Solution: A Kinetic Study

et al. 2014

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“…Because the Cbl that was added to the rabbit chow was free of Cbl analogues (9), we wondered if other components of the chow might have interacted with the added Cbl and converted some of it to Cbl analogues during the preparation or storage of the chow. A number of studies in the literature (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) have reported that various vitamins and minerals can "destroy" Cbl under certain conditions. Because of this, we investigated the possibility that Cbl analogues might be present in multivitamin and multivitamin-mineral pills.…”

Section: Introductionmentioning

confidence: 99%

Presence and formation of cobalamin analogues in multivitamin-mineral pills.

Kondo¹,

Binder²,

Kolhouse³

et al. 1982

J. Clin. Invest.

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A B S T R A C T Because the origin of cobalamin (vitamin B12) analogues in animal chows and animal and human blood and tissues is unknown, we investigated the possibility that multivitamin interactions might convert cobalamin to cobalamin analogues. We homogenized three popular multivitamin-mineral pills in water, incubated them at 37°C for 2 h, and isolated the cobalamin. Using paper chromatography we observed that 20-90% of the cobalamin was present as cobalamin analogues. Studies using cobalamin showed that these analogues were formed due to the concerted action of vitamin C, thiamine, and copper on CN-cobalamin. These cobalamin analogues are absorbed from the gastrointestinal tract of mice and either fail to stimulate or actually inhibit cobalamindependent enzymes when injected parenterally.We conclude that CN-cobalamin can be converted to potentially harmful cobalamin analogues by multivitamin-mineral interactions and that these interactions may be responsible for the presence of cobalamin analogues in animal chows and animal and human blood and tissues.

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“…An incompatibility of VB12 and VC in aqueous solutions has been reported. [1][2][3][4][5][6][7] However, it has not been fully elucidated how to stabilize these vitamins in a mixed solution yet. Many researchers have investigated the effect of VC on the stability of VB12 or cobalamin analogues in solution.…”

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confidence: 99%

Effect of Various Halide Salts on the Incompatibility of Cyanocobalamin and Ascorbic Acid in Aqueous Solution

et al. 2005

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Cyanocobalamin (VB12) and ascorbic acid (VC), both water-soluble vitamins, are essential nutrients involved in many physiological functions. These vitamins are extensively used in many pharmaceutical preparations and dietary supplements. An incompatibility of VB12 and VC in aqueous solutions has been reported. [1][2][3][4][5][6][7] However, it has not been fully elucidated how to stabilize these vitamins in a mixed solution yet. Many researchers have investigated the effect of VC on the stability of VB12 or cobalamin analogues in solution. [8][9][10][11][12] Most of them have focused only on the VB12 degradation, but not on VC. While Bartilucci et al. 6,7) have reported the interaction of VB12 and VC mixed condition in aqueous solutions evaluated by less sensitive methods, microbiological method for VB12 and titration for VC.In the present study, we determined the stabilities of VB12 and VC in acetate buffer using high performance liquid chromatography (HPLC), which shows better accuracy and precision than microbiological method and titration. The effects of halide salts on the stabilities of these vitamins in the buffer were also studied for the improvement of their stability. ExperimentalMaterials and Reagents VC and VB12 regulated by Japanese Pharmacopoeia were obtained from BASF Takeda Vitamins (Tokyo, Japan) and Aventis Pharma S.A. (Alsace, France), respectively. All other chemicals were purchased commercially. Water purified through a Milli-Q Labo (Millipore, Bedford, MA, U.S.A.) water system was used for all dilutions and sample preparations.Determination of VB12 Using HPLC An LC-10AVP system (Shimadzu, Kyoto, Japan) equipped with SIL-10ADVP auto-injector, SPD-10AVVP detector, LC-10ADVP pump, DGU-14A degasser, CTO-10ACVP column oven and C-R6A data processor was used to determine VB12 in the solutions. The HPLC conditions were as follows: column, 150ϫ4.6 mm TSK gel ODS-80TsQA (Tosoh, Tokyo, Japan); column temperature, 25°C; detection wavelength, 361 nm; mobile phase, acetonitrile-50 mM acetate buffer, pH 4.5 (13 : 87, v/v); flow rate, 1.0 ml/min; injection volume, 50 ml. Sample mixtures were directly injected into HPLC.Determination of VC Using HPLC An LC-10AVP system, the same composition system as described above, was used. The HPLC conditions were as follows: column, 150ϫ6 mm YMC pack ODS-AQ312 (YMC, Kyoto, Japan); column temperature, 25°C; detection wavelength, 290 nm; mobile phase, water-methanol-200 mM phosphate solution, pH 3.5 (8 : 1 : 1, v/v/v); flow rate, 1.0 ml/min; injection volume, 5 ml. Samples for HPLC analysis were prepared as follows: 0.3 ml of sample mixtures were transferred to vials for HPLC followed by adding 0.3 ml of 3% metaphosphoric acid containing 2% hydrochloric acid. The mixtures were analyzed immediately by HPLC.Influence of VC on VB12 Stability Various concentrations of VC (0, 1, or 5 mM) with 0.25 mM VB12 in 100 mM ammonium acetate-acetic acid buffer (pH 4.8) were prepared in a 12-ml brown glass vial with cap, and the mixtures were kept at room temperature for 8 h. The conce...

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Differential Stability of Various Analogs of Cobalamin to Vitamin C

Cited by 37 publications

References 5 publications

Effect of Ascorbic Acid on the Degradation of Cyanocobalamin and Hydroxocobalamin in Aqueous Solution: A Kinetic Study

Effect of Ascorbic Acid on the Degradation of Cyanocobalamin and Hydroxocobalamin in Aqueous Solution: A Kinetic Study

Presence and formation of cobalamin analogues in multivitamin-mineral pills.

Effect of Various Halide Salts on the Incompatibility of Cyanocobalamin and Ascorbic Acid in Aqueous Solution

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