A Comparison of the Stability of Cyanocobalamin and Its Analogs in Ascorbate Solution**Merck Sharp &amp; Dohme Research Laboratories, Rahway, N. J.

Hutchins, Hastings H.; Cravioto, Patricia J.; Macek, Thomas J.

doi:10.1002/jps.3030451211

Cited by 18 publications

(7 citation statements)

References 5 publications

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“…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). 3,3-Dimethyl-2,5-dioxopyrrolidine-4-propionamide and 3,3-dimethyl-2,5-dioxopyrrolidine-4-propionic acid have been identified as the oxidation products of B 12 (33).…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…Since the 2–3 mg of vitamin B12 (B12) typically present in the healthy human adult is provided exclusively by diet, B12 dietary intakes ranging from 0.4 μg day −1 (infants) to 5.5 μg day −1 (lactating women) have been recommended to prevent the adverse effects associated with a dietary B12 deficiency (Allen et al ., 2010; German Federal Institute for Risk Assessment, 2021; Vincenti et al ., 2021; National Institutes of Health, 2022). One strategy for achieving the recommended intakes, and thereby overcoming the three main causes of B12 deficiency – low intake of animal‐derived food, age‐related malabsorption of food‐bound B12, and pernicious anaemia – is the fortification of foods and dietary supplements with synthetic, crystalline cyanocobalamin (CN‐B12), the most stable form of B12, and the form commonly used for fortification (Hutchins et al ., 1956; Allen et al ., 2010; Nakos et al ., 2017; Lie et al ., 2019; Schnellbaecher et al ., 2019; Vincenti et al ., 2021). An example of a CN‐B12‐fortified food is infant formula, which is required by the U.S. Food and Drug Administration to contain ≥0.15 μg of B12 per 100 kcal (Code of Federal Regulations, U.S. Food and Drug Administration, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Factors capable of promoting B12 loss and thereby matrix variability include (in addition to the heat, oxygen, and B12 molecular form mentioned above) light, pH, reducing agents (including ascorbic acid, thiols, polyphenols, bisulfite, reducing sugars, ferrous salts), oxidising agents (including reactive oxygen species), other vitamins and/or decomposition products thereof, and sucrose (Hutchins et al ., 1956; Dolphin et al ., 1963; Ichikawa et al ., 2005; Ramasamy et al ., 2012; Ahmad et al ., 2014; Monajjemzadeh et al ., 2014; Salnikov et al ., 2014; Johns et al ., 2015; Dereven'kov et al ., 2016; Nakos et al ., 2017; Rempel et al ., 2018; Lie et al ., 2019; Schnellbaecher et al ., 2019; Salnikov et al ., 2021; Lee et al ., 2022).…”

Section: Introductionmentioning

confidence: 99%

Effects of metal ions on cyanocobalamin stability in heated milk protein‐based matrices

Ding

Choy

Chew

et al. 2022

Int J of Food Sci Tech

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Summary Losses of vitamin B12 during the processing and/or storage of foods and supplements have been associated with both reducing and oxidising agents. We evaluated the effects of six redox active (Cu2+, Fe2+, Fe3+, Mn2+, Ce3+, and Cr6+) and one redox inactive (Zn2+) metal ions on cyanocobalamin stability in heat‐treated, milk protein‐based matrices. The metal ion could either decrease (by ≤76%) or increase (by ≤56%) cyanocobalamin loss, depending on metal ion concentration and redox potential, as well as on matrix properties (metal ion binding, redox activity, and reactive oxygen species generation) and on protein properties (cysteine content, conformation, and charge density). The largest losses of cyanocobalamin appeared to be caused by redox cycling mechanisms (for Cu2+ and Fe2+); however, indications were that such losses could be mitigated by metal ion modification of the matrix. Only the redox inactive metal ion Zn2+ inhibited cyanocobalamin loss in all experimentally evaluated matrices.

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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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A Comparison of the Stability of Cyanocobalamin and Its Analogs in Ascorbate Solution**Merck Sharp & Dohme Research Laboratories, Rahway, N. J.

Cited by 18 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

Effects of metal ions on cyanocobalamin stability in heated milk protein‐based matrices

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

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