Tesis sobre el tema "Vitamin Solutions"

Oral vitamin K is administered to patients who have very high INR lab values and are on warfarin therapy. Due to the inability of some patients to swallow tablets, and the commercial formulation of vitamin K being available only as a tablet or an injectable emulsion, it may be necessary to compound an oral liquid formulation. When compounding batches of oral solutions, it is sometimes convenient to measure the product in unit doses. In this project, we compared liquid vitamin K in sterile water (1mg/mL) verses liquid vitamin K in Ora-Sweet (1mg/mL) stored in amber plastic syringes. Vitamin K is light sensitive and is best stored in amber containers. Vitamin K is also lipophilic and may adsorb to the plastic syringes. In this study, we investigated the feasibility of bulk compounding oral vitamin K solutions, and aliquoting them for storage in amber plastic syringes. The Vitamin K in sterile water syringes were made by mixing 45 mL of sterile water and 5 ampules, each containing 10mg/mL of vitamin K emulsion, together in an amber glass bottle for a final concentration of 1mg/mL. Thirty 1mL plastic amber syringes were filled with the mixture, capped, and placed in the refrigerator. The same process was repeated using Ora-Sweet instead of sterile water to fill thirty more plastic amber syringes. Three syringes of vitamin K in sterile water mixture, three syringes of vitamin K in Ora-Sweet mixture, and one Vitamin K reference standard were all analyzed using HPLC-UV on the day of compounding, and at day 1, 2, 4, 7, 14, 21, 30, 60, and 90. If stability is defined as 90-110% active ingredient, then Vitamin K in sterile water is stable to fourteen days, 95.3±3.5% recovery, but some samples fell below 90% recovery after 14 days. By day ninety, the recovery in SWFI syringes was 84.2±8.9%. For vitamin K in Ora-Sweet, the within-day variability was very high due to limitations in drug dissolution; as such the average concentration was not consistently above 90%. On the day of compounding, the percent recovery in the Ora-Sweet syringes was 92.7±9.9%, despite 1 hour of stirring. In conclusion, the Vitamin K in sterile water mixture can be stored in refrigerated, amber oral plastic syringes for 14 days, but plastic amber syringes were not appropriate for storage of the Vitamin K in Ora-Sweet mixture.

Purpose: Vitamin K1 (phytonadione) is a fat-soluble vitamin and an essential cofactor for the synthesis of clotting factors II, VII, IX, X, protein C, and protein S. Vitamin K antagonists deplete vitamin K reserves effectively preventing the synthesis of these clotting factors leading to anticoagulation. Overly excessive anticoagulation, as evidenced by INRs greater than 5, may necessitate vitamin K for reversal of warfarin depending on bleeding risk factors. For elevated INR without bleeding, the oral route is preferred. Orally administered vitamin K1 tablets are only supplied by a single manufacturer, and only available as a 5 mg tablet. Concerns with availability of this tablet, lack of dosing options for treatment requiring less than 5 mg, and delivery options for patients unable to swallow whole tablets have prompted the exploration of alternative dosing strategies using the 10 mg/mL injectable emulsion compounded into an oral liquid. The possibility of storing the oral liquid in unit-doses adds a layer of convenience, and is common practice in many hospital pharmacies. In this project, we compared oral liquid vitamin K1 in sterile water for injection (SWFI) to oral liquid vitamin K1 in Ora-Sweet, simple syrup, cherry syrup, and Syrpalta stored in amber plastic oral syringes. Methods: Batches of 1 mg/mL vitamin K1 were prepared in SWFI, Ora-Sweet, simple syrup, cherry syrup, and Syrpalta and drawn up by 1-mL aliquots into amber plastic oral syringes. Syringes were capped and stored in a laboratory refrigerator (4.9-5.4oC). for the duration of the study. On each study day (0, 1, 2, 4, 7, 14, 21, 30, 60, and 90), three syringes from each vehicle were removed, and the contents diluted with ethanol to achieve a 0.5 mg/mL assay concentration. Additionally, USP reference material was used on each study day to prepare a fresh 0.5 mg/mL reference solution. The samples and reference were analyzed using a previously validated HPLC-UV method. Results were compared using a 2-way ANOVA (p = 0.05) with post-hoc Tukey’s correction for multiple comparisons. Product stability was defined as 90-110% labeled amount. Results: Of the vehicles tested, SWFI was the most suitable vehicle for longer-term storage of unit-dosed vitamin K1. The 1 mg/mL vitamin K1 in SWFI, when stored in amber plastic oral syringes, remains within the acceptable 90 – 110% range for 21 days. The Syrpalta preparation demonstrated the next highest BUD of 7 days, with one syringe (2 injections) falling outside the 90% potency at the 14 day time point. Cherry syrup allowed for very limited stability, with a BUD of 24 hours. By the 48-hour time point, two of the three samples were below the 90% potency cutoff. For the vitamin K oral solutions prepared in simple syrup and Ora-Sweet, the recovery of vitamin K was not within acceptable limits, even on the day of compounding. The initial recovery for vitamin K in simple syrup was only 86.8%. Similarly, the preparation in Ora-Sweet, was not at acceptable potency on the day of compounding, (92.7 ± 9.9%). While the average recovery in Ora-Sweet exceeded 90%, the variability between samples suggests a lack of homogeneous distribution of drug through the vehicle. Statistically significant differences were detected between the SWFI preparation and all other vehicles in a 2-way ANOVA with Tukey’s multiple comparison post-test (p-value of 0.05). This difference was most pronounced between SWFI and Ora-Sweet and SWFI and simple syrup (both p < 0.0001). Cherry syrup was also vastly different from SWFI (p = 0.0002), and the difference between SWFI and Syrpalta was less pronounced, yet still significant (p = 0.0442). Conclusion: Vitamin K1 in sterile water and Syrpalta was stable for 21 days and 7 days, respectively, when stored in amber plastic syringes. Vitamin K1 in cherry syrup was only stable for 24 hours in the syringes. For vitamin K1 in Ora-Sweet and simple syrup, the within-day variability was very high due to limitations in drug dissolution; as such the average recovery was not consistently above 90%, even on the day of compounding. Statistically significant differences were detected between the SWFI formulation and all other vehicles. Several factors appear to affect the potency and stability of vitamin K1 in different vehicles. Because the stability of vitamin K1 oral solution differs between storage in amber glass bottles and oral syringes, vitamin K1 may have the potential to adsorb to polypropylene (PPE). The pH of the vehicle may contribute to degradation of vitamin K1, and the viscosity of the vehicle may affect the achievable potency of certain mixtures. The viscosity of the mixture also appears to affect maintenance of a homogenous mixture, but the presence of alcohol in the vehicle may help aid in solubilizing the vitamin K1 in Syrpalta. Vitamin K1 in SWFI appears to be the most suitable vehicle for longer-term storage of unit-dosed vitamin K, but Syrpalta and cherry syrup may also be appropriate for more immediate use.

We have synthesized asymmetric di- and triblock copolymers containing chemically complementary blocks of poly(acrylic acid) and methoxypoly(ethylene oxide) (PAAc-b-MOPEO) or poly(ethylene oxide) (PAAc-b-PEO-b-PAAc) using a template radical block copolymerization process. At low pH, polyacid blocks of these copolymers were protonated and formed the intramolecular polycomplexes (IntraPCs) with MOPEO or PEO blocks. Due to both the intramolecular complex formation and hydrophobic interactions between non-polar bound segments of the blocks, an intensive micellization in copolymer solutions at low pH took place. Aqueous copolymer solutions were used as nanocontainers for encapsulation of poorly soluble vitamin E and as nanoreactors for the silver nanoclusters/nanoparticles formation. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/34943

A linear differential operator L is called weakly hypoelliptic if any local solution u of Lu = 0 is smooth. We allow for systems, i.e. the coefficients may be matrices, not necessarily of square size. This is a huge class of important operators which covers all elliptic, overdetermined elliptic, subelliptic and parabolic equations. We extend several classical theorems from complex analysis to solutions of any weakly hypoelliptic equation: the Montel theorem providing convergent subsequences, the Vitali theorem ensuring convergence of a given sequence, and Riemann's first removable singularity theorem. In the case of constant coefficients we show that Liouville's theorem holds, any bounded solution must be constant and any L^p solution must vanish.

Ces travaux de recherche ont permis d ' élaborer une méthode de gélification 'à froid ' induite par l'addition de sels de calcium à des protéines de soya thermiquement dénaturées, le but ultime étant d'utiliser ces hydrogels dans le développement de nouveaux aliments fonctionnels et comprimés nutraceutiques ayant des effets bénéfiques sur la santé. Les résultats obtenus démontrent la formation de deux types d 'hydrogels distincts selon la teneur en sels de calcium utilisés. À faible teneur en sels de calcium, des hydrogels filamenteux caractérisés par une microstructure ordonnée et une bonne capacité de rétention d'eau sont obtenus, alors que des hydrogels poreux, agrégés et ayant une faible capacité de rétention d'eau sont identifiés lorsqu'une haute teneur en sels de calcium est utilisée. Ces deux types d 'hydrogels démontrent des propriétés rhéologiques distinctes, utilisées pour quantifier leur dimension fractale respective. Il a été démontré par cette étude que les hydrogels de type filamenteux sont sujet à un mécanisme de formation lent selon un patron dicté par l'encombrement stérique des agrégats primaires, tandis que les hydrogels agrégés sont formés rapidement de façon totalement aléatoire, créant une microstructure désordonnée. Des études in vitro en conditions gastro-intestinales montrent clairement la capacité des hydrogels filamenteux et agrégés à protéger des molécules de vitamine B2, emprisonnées dans leur structure, contre les conditions gastriques (enzymes digestives, pH acide) et à les libérer en conditions intestinales. Les hydrogels filamenteux montrent des profils de libération de la vitamine B2 plus constants que ceux agrégés dû à leur structure moins poreuse. Des comprimés formés à partir des hydrogels lyophilisés et compressés ont également été conçus. Les études in vitro effectuées sur ces comprimés démontrent, comme les études menées sur les hydrogels, une bonne protection de la vitamine B2 en présence de conditions gastriques et une libération accrue lorsque soumis aux conditions intestinales. D'intéressantes perspectives dans le développement de véhicules (hydratés ou comprimés) pour la protection de molécules nutraceutiques et leur libération intestinale sont donc envisageables à partir des hydrogels développés dans le cadre de cette étude.

Cette thése concerne l'existence et la régularité de solutions d'équations non-linéaires elliptiques, d'équations paraboliques et d'équations de Hesse avec mesures, et les critéres de l'existence de solutions grandes d'équations elliptiques et paraboliques non-linéaires. \textbf{Liste de publications} \begin{description} \item[1.] Avec M. F. Bidaut-Véron, L. Véron; {\em Quasilinear Lane-Emden equations with absorption and measure data,} Journal des Mathématiques Pures et Appliquées,~{\bf 102}, 315-337 (2014). \item[2] Avec L. Véron; {\em Quasilinear and Hessian type equations with exponential reaction and measure data,} Archive for Rational Mechanics and Analysis, {\bf 214}, 235-267 (2014). \item[3] Avec L. Véron; {\em Wiener criteria for existence of large solutions of quasilinear elliptic equations with absorption,} 17 pages, soumis, arXiv:1308.2956. \item[4] Avec M. F. Bidaut-Véron; {\em Stability properties for quasilinear parabolic equations with measure data,} 29 pages, á apparaître dans Journal of European Mathematical Society, arXiv:1409.1518. \item[5] Avec M. F. Bidaut-Véron; {\em Evolution equations of $p$-Laplace type with absorption or source terms and measure data}, 21 pages, á apparaître dans Communications in Contemporary Mathematics, arXiv:1409.1520. \item[6] {\em Potential estimates and quasilinear parabolic equations with measure data,} 118 pages, arXiv:1405.2587v1. \item[7] Avec L. Véron; {\em Wiener criteria for existence of large solutions of nonlinear parabolic equations with absorption in a non-cylindrical domain,} 29 pages, soumis,\\ arXiv:1406.3850. \item[8] Avec M. F. Bidaut-Véron; {Pointwise estimates and existence of solutions of porous medium and $p$-Laplace evolution equations with absorption and measure data,\em } 27 pages, soumis, arXiv:1407.2218. \end{description}\begin{description} \item[1.] Avec M. F. Bidaut-Véron, L. Véron; {\em Quasilinear Lane-Emden equations with absorption and measure data,} Journal des Mathématiques Pures et Appliquées,~{\bf 102}, 315-337 (2014). \item[2] Avec L. Véron; {\em Quasilinear and Hessian type equations with exponential reaction and measure data,} Archive for Rational Mechanics and Analysis, {\bf 214}, 235-267 (2014). \item[3] Avec L. Véron; {\em Wiener criteria for existence of large solutions of quasilinear elliptic equations with absorption,} 17 pages, soumis, arXiv:1308.2956. \item[4] Avec M. F. Bidaut-Véron; {\em Stability properties for quasilinear parabolic equations with measure data,} 29 pages, á apparaître dans Journal of European Mathematical Society, arXiv:1409.1518. \item[5] Avec M. F. Bidaut-Véron; {\em Evolution equations of $p$-Laplace type with absorption or source terms and measure data}, 21 pages, á apparaître dans Communications in Contemporary Mathematics, arXiv:1409.1520. \item[6] {\em Potential estimates and quasilinear parabolic equations with measure data,} 118 pages, arXiv:1405.2587v1. \item[7] Avec L. Véron; {\em Wiener criteria for existence of large solutions of nonlinear parabolic equations with absorption in a non-cylindrical domain,} 29 pages, soumis,\\ arXiv:1406.3850. \item[8] Avec M. F. Bidaut-Véron; {Pointwise estimates and existence of solutions of porous medium and $p$-Laplace evolution equations with absorption and measure data,\em } 27 pages, soumis, arXiv:1407.2218. \end{description}

碩士
中原大學
化學研究所
89
Abstract We have studied two surfactants: Sodium dodecyl sulfate and Dodecyltrimethyl ammonium bromide and five electrolytes: NaCl、KCl、CaCl2、NaNO3 and Na2SO4. Vitamin E dissolution in surfactant solutions can be largely increased by adding electrolyte(saturation value＞1). Stability of emulsion is also improved. In this study, we used dynamic light scattering、UV absorption、turbidity and visual observation to study the influence of an electrolyte on emulsion systems. The CMC and MDC of many surfactant solutions shift to the lower concentration by adding electrolytes and the solubilization curves moves to lower surfactant concentrations which is more suitable for some applications.

博士
中原大學
化學研究所
92
Fat-soluble vitamins have been extensively used in the preparation of medical, food and cosmetic products. To significantly increase the solubility of vitamin E, a series of bile salts, anionic, cationic and zwitterionic surfactants in electrolyte sodium chloride (NaCl) is used. Similarly using Huls B433, a commercial surfactant system to use in crude oil enhanced oil recovery, increases the solubility of vitamin K1. This research studies the effect of electrolyte-added surfactant solution on the emulsion, using techniques including dynamic light scattering, Ultraviolet absorption spectroscopy, turbidity, and visual observation. The study provides a further understanding of the dissolved vitamin E and vitamin K1. There an optimum electrolyte concentration of the exists solution to increase solubility of vitamin E and K1. The dissolution of vitamin K1 and its decrease in interfacial tension with the Huls B433 surfactant system follows both the experimental rules of crude oil and the preferred larger surfactant micelles.

Introduction : Chez les nouveau-nés prématurés, l’hyper-alimentation intraveineuse (HAIV) contribue à leur survie, mais elle est aussi une source importante de molécules oxydantes. L’absence d’une protection adéquate contre la lumière ambiante génère in vitro, via la photo-excitation de la riboflavine, du H2O2, des peroxydes organiques et un dérivé peroxydé de la vitamine C, l’ascorbylperoxyde (AscOOH). Plusieurs données du laboratoire associent l’infusion d’HAIV à des désordres lipidiques dans notre modèle animal. L’hypothèse est donc que l’AscOOH a un pouvoir oxydant et est responsable de certains des effets biologiques observés. Mes objectifs sont les suivants : 1) développer une méthode de dosage de l’AscOOH; 2) démontrer, à l’aide du modèle animal bien établi au laboratoire, des relations entre la concentration tissulaire de cette molécule et des paramètres métaboliques et l’état redox au foie et dans la circulation; et 3) confirmer l’effet physiologique de l’AscOOH dans un modèle cellulaire. Méthode : Différents étalons internes potentiels ont été testés pour le dosage de l’AscOOH par spectrométrie de masse après séparation sur HPLC (LC-MS). Les phases mobiles et conditions chromatographiques ont été optimisées. Pour l’objectif 2, des cobayes de 3 jours de vie (n=11) ont reçu par voie intraveineuse une dose d’AscOOH (entre 0 et 3,3mM). Les animaux ont été sacrifiés au 4e jour de traitement pour le prélèvement de tissus. Les concentrations tissulaires d’AscOOH ont été déterminées au LC-MS. La triglycéridémie et la cholestérolémie ont été mesurées à l’aide d’un kit commercial par spectrophotométrie. Le glutathion oxydé et réduit ont été mesurés par électrophorèse capillaire. Les relations linéaires obtenues sont exprimées par le ratio des carrés (r2), et traitées par ANOVA. Résultats : La validation du dosage de l’AscOOH par LC-MS a été réalisée. Chez les animaux, la concentration urinaire d’AscOOH par créatinine corrèle positivement avec la dose reçue, négativement avec la lipidémie, et négativement avec le redox sanguin et érythrocytaire, indiquant un milieu moins oxydé. Conclusion : La concentration urinaire d’AscOOH peut donc être un reflet de l’oxydation de l’HAIV en clinique. Nos données chez l’animal suggèrent une interaction de l’AscOOH avec le métabolisme hépatique produisant une chute de la concentration plasmatique de cholestérol et de triglycérides. Le modèle cellulaire n’a pas permis d’élucider le mécanisme moléculaire de l’action de l’AscOOH sur le métabolisme.
Introduction: Intravenous hyperalimentation (IVHA) often contributes to the survival of preterm newborns, but it is also an important source of oxidizing molecules. The lack of adequate protection from ambient light generates, in vitro, through the photo-excitation of riboflavin, H2O2, organic peroxides and a peroxidated derivative of vitamin C: ascorbylperoxide (AscOOH). Certain data from our laboratory linked the infusion of IVHA to lipid disorders in our animal model. The hypothesis is that AscOOH is an oxidant that is responsible for some of the biological effects observed. My objectives are: 1) to develop a method for quantitation of AscOOH, 2) to demonstrate, using the guinea pig model used by our laboratory, relations between the tissue concentration of this molecule and metabolic and redox parameters in the liver and plasma, and 3) to confirm the physiological effect of AscOOH in a cell culture model. Method: Different promising internal standards were tested for AscOOH quantitation by mass spectrometry after HPLC separation (LC-MS). Mobile phases and chromatography conditions have been optimized. For objective #2, 3 days old guinea pig pups (n = 11) received an intravenous dose of AscOOH (between 0 and 3.3mM). Animals were sacrificed on the 4th day of treatment for tissue gathering. Tissues AscOOH concentrations were determined by LC-MS. The triglyceride and cholesterol levels were measured by spectrophotometry using a commercial kit. The oxidized and reduced glutathione were measured by capillary electrophoresis. The linear relations obtained are expressed by the square of the correlation coefficient (r2), and processed by ANOVA. Results: The validation of the LC-MS method for AscOOH quantification has been achieved. In animals, the concentration of urinary AscOOH by creatinine correlates positively with the dose received, negatively with blood lipids, and negatively with blood and erythrocyte redox, indicating a less oxidized environment. Conclusion: The urinary AscOOH concentration may be a good indicator of the oxidation state of clinical IVHA. Our data in animals suggest an interaction between AscOOH and liver metabolism producing a drop in plasma concentration of cholesterol and triglycerides. The cell model was not able to clarify the molecular mechanism of AscOOH action on metabolism.

Student Number : 0010064D - MSc dissertation - School of Chemistry - Faculty of Science
This dissertation describes the synthesis, physical characterisation and solution chemistry of NAc-CoIIIMP8, a biomimetic model compound of vitamin B12a, synthesised from the haemoctapeptide derived from horse heart cytochrome c. Peptic and tryptic digestion of horse heart cytochrome c removes much of the globular protein encapsulating the iron porphyrin prosthetic group. The resulting haemoctapeptide fragment retains residues 14 to 21 of the parent cytochrome (MP8) via thioether linkages to Cys-14 and Cys-17. Reductive demetalation of MP8 yielded the metal free MP8. This was treated with cobaltous acetate in an aerated aqueous solution to produce CoIIIMP8. CoIIIMP8 was acetylated by treatment with acetic anhydride and yielded N-acetyl-Co(III)- microperoxidase 8 (NAc-CoIIIMP8). It is well established that acetylation reduces aggregation of these haempeptides. The starting materials and products of each step during synthesis were characterised by UV-visible absorption spectroscopy, high performance liquid chromatography (HPLC) and fast atom bombardment-mass spectroscopy (FAB-MS). MP8 free base and Co(III)-MP8 were also analysed using luminescence spectroscopy. The molar extinction coefficients of NAcCoIII-MP8 in aqueous and ionic medium were determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and UV- visible absorption spectroscopy. The extinction coefficient, e, of NAcCoIIIMP8 (? = 420 nm, pH 7.00, 25 ºC) in distilled water and 1.0 M NaClO 4 was 1.80 + 0.01 x 105 M-1 cm-1 and 1.66 + 0.01 x 105 M-1 cm-1, respectively. Beer’s law studies show that NAc-CoIIIMP8 remains monomeric in aqueous solution up to concentrations of at least 35 μM. The spectroscopic changes observed for NAc-CoIIIMP8 during the course of a spectrophotometric titration are very similar to those observed for NAc-FeIIIMP8, with both being consistent with six successive ionisations. By analogy with NAc-FeIIIMP8, we attributed the first (pK1 = 2.0 + 0.3) to the coordination of the c-terminal carboxylate group (Glu-21) of the appended polypeptide. The second acid range transition (pK2 = 2.8 + 0.1) for NAcCoIIIMP8 involved the deprotonation of the cationic His-18 and concomitant replacement of the c-terminal carboxylate by the neutral heterocyclic base. The third and fourth pKa’s are attributed to the ionisation of the haem propanoic acid groups (pK3 = 3.9 + 0.03) and (pK4 = 7.5 + 0.03). Ionisation of the cobalt-bound water molecule above neutal pH was assigned to pK5 = 9.2 + 0.04. Finally, we attributed pK6 (12.1 + 0.03) to the ionisation of the coordinated histidine trans to the OH- to form the histidinate complex (His--CoIII-OH-). A principal aim of this work was to demonstrate that the kinetics and the thermodynamics of the ligand substitution reactions of NAc-CoIIIMP8 can be studied spectrophotometrically; a comprehensive investigation of these reactions will be undertaken by othe rs. Towards this end the formation constants between NAc-CoIIIMP8 and N- methylimidazole and pyridine were determined. We observed the formation of a bis-substituted complex in the reaction of NAc-CoIIIMP8 with the ligands, but only mono-substitution with NAc-FeIIIMP8 and B12a. We attribute this first ligand binding to the replacement of the axial water molecule, and the second replacement of the axial histidine residue. The absence of the second reaction with NAc-FeIIIMP8 and B12a suggest that the CoIII-N(His) bond in NAc-CoIIIMP8 is significantly weaker than the FeIIIN( His) and CoIII-N(dimethylbenzimidazole) bond, respectively. When comparing the formation constants of NAc-FeIIIMP8, NAc-CoIIIMP8 and B12a, we found that the value of log K1 for NAc-CoIIIMP8 for these ligands is significantly higher than that reported for NAc-FeIIIMP8 and B12a. Kinetics studies of NAc-CoIIIMP8 with N-methylimidazole and methylamine were investigated. The data obtained did not follow conventional pseudo-first order kinetics; instead there was some evidence for biphasic kinetics. In the reaction of Nmethylimidazole with NAc-CoIIIMP8, we observed that the rate of reaction is virtually independent of the concentration of the incoming ligand. The results can be explained if the mechanism proceeds through a purely dissociative mechanism, i.e., if the rate of the reaction is controlled by the rate at which, firstly, the water molecule dissociates from the CoIII centre and, secondly, the histidine dissociates from the metal. The second order rate constant, k2, could not be determined since the rate of reaction is independent of Nmethylimidazole concentration. In the reaction of methylamine with NAc-CoIIIMP8, we observed that the rate of reaction is dependent on the concentration and participation of the incoming ligand. We propose that the displacement of water and histidine by methylamine involves an interchange mechanism (Id), where the bond forming and bond breaking occur simultaneously, and thus the rate of reaction becomes dependent on the concentration of the incoming ligand. The results showed that the rate of reaction for methylamine with NAc-CoIIIMP8 was faster than with N-methylimidazole. We attributed these differences in rate constants to the size of the incoming ligands. N-methylimidazole is a secondary amine and is relatively more bulky than methylamine which is a primary amine; therefore it is easier for methylamine to attach to the metal centre compared to N- methylimidazole. For comparison, the rate of reaction of B12a with N-methylimidazole and methylamine was determined. The results show that the rate of the reaction between NAc-CoIIIMP8 and B12a with N-methylimidazole and methylamine are significantly different. Furthermore, we observe only mono -substitution in B12a and bisubstitution in NAc- CoIIIMP8. Overall, the results presented in this work do give a general indication on how thermodynamically stable a CoIII ion is in a porphyrin ring and also to a very limited extent show that a porphyrin does not confer the same kinetic lability on the CoIII ion as the corrin ring.