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

Ahmad, Iqbal; Qadeer, Kiran; Zahid, Saima; Sheraz, Muhammad Ali; Ismail, Tehmina; Hussain, Waqar; Ansari, Izhar A

doi:10.1208/s12249-014-0160-5

Cited by 34 publications

(32 citation statements)

References 51 publications

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“…During subsequent storage, the vitamin B 12 form was found to be degraded by an additional 20%. In the presence of ascorbic acid, hydroxocobalamin is a known oxidation product of cyanocobalamin . However, our current method was unable to distinguish hydroxocobalamin from its unoxidized form.…”

Section: Resultsmentioning

confidence: 68%

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Effect of manufacturing temperature and storage duration on stability of chemically defined media measured with LC‐MS/MS

Krattenmacher

Heermann

Calvet

et al. 2018

J of Chemical Tech & Biotech

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BACKGROUND Chemically defined media (CDM) are used routinely in industrial settings for the production of biopharmaceuticals from mammalian cells, so attention has shifted to understanding their chemical behavior and impact on process robustness. In this context, one particular problem is the risk of cross reactivity and instability in complex mixtures of chemicals at high concentrations. RESULTS In order to characterize potentially unstable medium compounds in feed media, we developed and validated a novel liquid chromatography tandem mass spectrometry (LC‐MS/MS) method to simultaneously quantify the majority of medium compounds. We used this application advantage to provide the following insights into molecular processes occurring in CDM prepared at different temperatures and during storage: Concentration profiles of critical compounds in CDM are independent of preparation temperature and storage material but show significant alterations over time. In particular l‐cysteine, l‐proline, vitamin B6, thiamine and cyanocobalamin were found to be rather unstable. Using mixed mode chromatography allows expansion of the method to cover additional analytes of interest, as demonstrated by inclusion of seven additional CDM reaction products. CONCLUSION The successful development of a new LC‐MS/MS method allowed us to show the impact of storage duration on the stability of CDM compounds. Furthermore, the results suggest that essential parameters for medium preparation (e.g. temperature) and storage upscaling (e.g. vessel material) are not impacting upon the chemical composition of CDM. © 2018 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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Section: Resultsmentioning

confidence: 68%

“…In the presence of ascorbic acid, hydroxocobalamin is a known oxidation product of cyanocobalamin. 64 However, our current method was unable to distinguish hydroxocobalamin from its unoxidized form. As the cyanocobalamin concentration decrease is very pronounced (>60%), an impact on CDM performance is likely.…”

Section: Thiamine and Cyanocobalaminmentioning

confidence: 73%

Effect of manufacturing temperature and storage duration on stability of chemically defined media measured with LC‐MS/MS

Krattenmacher

Heermann

Calvet

et al. 2018

J of Chemical Tech & Biotech

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“…A one‐electron reduction by ascorbate produces vitamin B 12r , which then yields hydroxocobalamin via oxidation by air (Gakenheimer & Feller, ; Macek, ; Reddy, ; Trenner, Buhs, Bacher, & Gakenheimer, ). Degradation by ascorbate proceeds further, and it was shown that ascorbate‐mediated degradation of hydroxocobalamin occurs at a rate about 10x that of cyanocobalamin (Ahmad et al, ). This ascorbate‐mediated degradation is enhanced in the presence of Cu 2+ salts, and cyanocobalamin can also be degraded by the reduced form of ascorbic acid and dehydroascorbic acid (Bartilucci & Poss, ; Rosenberg, ).…”

Section: Cyanocobalaminmentioning

confidence: 99%

Vitamins in cell culture media: Stability and stabilization strategies

Schnellbaecher

Binder

Bellmaine

et al. 2019

Biotech & Bioengineering

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Nowadays, chemically defined cell culture media (CCM) have replaced serum‐ and hydrolysate‐based media that rely on complex ingredients, such as yeast extracts or peptones. Benefits include a significantly lower lot‐to‐lot variability, more efficient manufacturing by reduction to essential components, and the ability to exclude components that may negatively influence growth, viability, or productivity. Even though current chemically defined CCMs provide an excellent basis for various mammalian biotechnological processes, vitamin instabilities are known to be a key factor contributing to the variabilities still present in liquid CCM as well as to short storage times. In this review, the chemical degradation pathways and products for the most relevant vitamins for CCM will be discussed, with a focus on the effects of light, oxygen, heat, and other CCM compounds. Different approaches to stabilize vitamins in solution, such as replacement with analogs, encapsulation, or the addition of stabilizing compounds will also be reviewed. While these vitamins and vitamin stabilization approaches are presented here as particular for CCM, the application of these concepts can also be considered relevant for pharmaceutical, medical, and food supplement purposes. More precise knowledge regarding vitamin instabilities will contribute to stabilize future formulations and thus decrease residual lot‐to‐lot variability.

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“…Ascorbate promoted the degradation of B 12 in the solution. Ahmad et al ( Ahmad et al, 2017/01 ), ( Ahmadet aleng, 2014 ) described the degradation product as hydroxocobalamin, which is further rapidly degraded to products that do not elicit the vitamin functions. The degradation of cyanocobalamin to hydroxocobalamin involves the loss of the CN-group.…”

Section: Discussionmentioning

confidence: 99%

Quadruple fortification of salt for the delivery of iron, iodine, folic acid, and vitamin B12 to vulnerable populations

Modupe

Diósady

2021

Journal of Food Engineering

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A process for simultaneous delivery of iron, iodine, folic acid, and vitamin B 12 through salt as a potential and holistic approach to ameliorate anaemia and reduce maternal and infant mortality is presented. Two approaches for adding folic acid and B 12 to salt during double fortification with iron and iodine were investigated. Attempts to add both micronutrients through the iodine spray solution were unsuccessful. Hence, folic acid was added through a stabilized iodine solution, and B 12 was added through the iron premix. Four approaches used to incorporate B 12 into the iron premix were investigated: (1) co-extruding B 12 with iron, (2) spraying B 12 on the surface of the iron extrudate, (3) adding B 12 to the colour masking agent, and (4) adding B 12 to the outer coating. Of these approaches, coextrusion (1) was the best, based on the ease of production and stability of fortificants. The salt formulated with the solid iron-B 12 premix and sprayed iodine and folic acid solution contained 1000 ppm iron, 50 ppm iodine, 25 ppm folic acid, and 0.25 ppm B 12 . Over 98% of B 12 , 93% folic acid, and 94% iodine were retained after 6-month storage in the best formulation. This technology can simultaneously deliver iron, iodine, folic acid, and vitamin B 12 in a safe and stable salt enabling public health measures for improved health at a minimal additional cost.

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

Cited by 34 publications

References 51 publications

Effect of manufacturing temperature and storage duration on stability of chemically defined media measured with LC‐MS/MS

Effect of manufacturing temperature and storage duration on stability of chemically defined media measured with LC‐MS/MS

Vitamins in cell culture media: Stability and stabilization strategies

Quadruple fortification of salt for the delivery of iron, iodine, folic acid, and vitamin B12 to vulnerable populations

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