scholarly journals Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3469 ◽  
Author(s):  
Brusač ◽  
Jeličić ◽  
Amidžić Klarić ◽  
Nigović ◽  
Turk ◽  
...  
Keyword(s):  
Folic Acid ◽  
Fixed Dose ◽  
Reliable Determination ◽  
Pharmaceutical Ingredients ◽  
Physico Chemical ◽  
Pharmacokinetic Properties ◽  
On Line ◽  
Inflammatory Bowel ◽  
Tablet Formulations

With the increase in the number of medicines patients have to take, there has been a rapid rise of fixed-dose combinations (FDCs) in the last two decades. Prior to FDC development, pharmacokinetic properties of active pharmaceutical ingredients (APIs) have to be evaluated, as well as methods for their determination developed. So as to increase patient compliance in inflammatory bowel disease, three novel FDCs of thiopurine immunosuppressants and folic acid are proposed; physico-chemical and pharmacokinetic properties such as hydrophobicity, lipophilicity and plasma protein binding of all APIs are evaluated. Moreover, experimental results of different properties are compared to those computed by various on-line prediction platforms so as to evaluate the viability of the in silico approach. A simultaneous method for their determination is developed, optimized, validated and applied to commercial tablet formulations. The method has shown to be fast, selective, accurate and precise, showing potential for reliable determination of API content in proposed FDCs during its development.

scholarly journals A chromatographic approach to development of 5-aminosalicylate/folic acid fixed-dose combinations for treatment of Crohn’s disease and ulcerative colitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mario-Livio Jeličić ◽  
Edvin Brusač ◽  
Daniela Amidžić Klarić ◽  
Biljana Nigović ◽  
Nikša Turk ◽  
...  
Keyword(s):  
Folic Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Fixed Dose ◽  
Disease Therapy ◽  
Inflammatory Bowel ◽  
Binding Percentage ◽  
States Pharmacopeia

AbstractMedication adherence is an important factor in inflammatory bowel disease therapy, which includes regular supplementation of malabsorbed vitamins. Absorption of folic acid is limited due to the damaging of the gastrointestinal tract, which can increase the chances to develop megaloblastic anaemia and colorectal cancer. In this work, 5-aminosalicylates (mesalazine, balsalazide, sulfasalazine and olsalazine) and folic acid were characterized regarding their pharmacokinetic related properties (hydrophobicity, phospholipid and plasma protein binding) using the biomimetic chromatographic approach. Despite the high binding percentage of 5-aminosalicylates for human serum albumin (> 61.44%), results have shown that folic acid binding to human serum albumin protein is far greater (69.40%) compared to α1-acid-glycoprotein (3.45%). Frontal analysis and zonal elution studies were conducted to provide an insight into the binding of folic acid to human serum albumin and potential competition with 5-aminosalicylates. The analytical method for the simultaneous determination of assay in proposed fixed-dose combinations was developed and validated according to ICH Q2 (R1) and FDA method validation guidelines. Separation of all compounds was achieved within 16 min with satisfactory resolution (Rs > 3.67) using the XBridge Phenyl column (150 × 4.6 mm, 3.5 µm). High linearity (r > 0.9997) and precision (RSD < 2.29%) was obtained, whilst all recoveries were within the regulatory defined range by British (100.0 ± 5.0%) and United States Pharmacopeia (100.0 ± 10.0%).

scholarly journals An Approach for Routine Analytical Detection of Beeswax Adulteration Using FTIR-ATR Spectroscopy

2015 ◽  
Vol 59 (2) ◽  
pp. 37-49 ◽  
Author(s):  
Lidija Svečnjak ◽  
Goran Baranović ◽  
Marko Vinceković ◽  
Saša Prđun ◽  
Dragan Bubalo ◽  
...  
Keyword(s):  
Ir Spectra ◽  
Beef Tallow ◽  
Predictive Power ◽  
Least Squares Regression ◽  
Chemical Parameters ◽  
Reliable Determination ◽  
Physico Chemical ◽  
Chemical Background ◽  
Atr Spectroscopy

Abstract Although beeswax adulteration represents one of the main beeswax quality issues, there are still no internationally standardised analytical methods for routine quality control. The objective of this study was to establish an analytical procedure suitable for routine detection of beeswax adulteration using FTIR-ATR spectroscopy. For the purpose of this study, reference IR spectra of virgin beeswax, paraffin, and their mixtures containing different proportions of paraffin (5 - 95%), were obtained. Mixtures were used for the establishment of calibration curves. To determine the prediction strength of IR spectral data for the share of paraffin in mixtures, the Partial Least Squares Regression method was used. The same procedure was conducted on beeswax-beef tallow mixtures. The model was validated using comb foundation samples of an unknown chemical background which had been collected from the international market (n = 56). Selected physico-chemical parameters were determined for comparison purposes. Results revealed a strong predictive power (R2 = 0.999) of IR spectra for the paraffin and beef tallow share in beeswax. The results also revealed that the majority of the analysed samples (89%) were adulterated with paraffin; only 6 out of 56 (11%) samples were identified as virgin beeswax, 28% of the samples exhibited a higher level of paraffin adulteration (>46% of paraffin), while the majority of the analysed samples (50%) were found to be adulterated with 5 - 20% of paraffin. These results indicate an urgent need for routine beeswax authenticity control. In this study, we demonstrated that the analytical approach defining the standard curves for particular adulteration levels in beeswax, based on chemometric modelling of specific IR spectral region indicative for adulteration, enables reliable determination of the adulterant proportions in beeswax.

scholarly journals Synthesis of new (arylcarbonyloxy)aminopropanol derivatives and the determination of their physico-chemical properties

2013 ◽  
Vol 11 (11) ◽  
pp. 1757-1767 ◽  
Author(s):  
Jan Tengler ◽  
Iva Kapustíková ◽  
Ondřej Stropnický ◽  
Petr Mokrý ◽  
Michal Oravec ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Beta Blockers ◽  
Chemical Properties ◽  
Weak Base ◽  
Chemical Parameters ◽  
Multistep Synthesis ◽  
Physico Chemical ◽  
Pharmacokinetic Properties ◽  
Receptor Beta

AbstractEight hydrochlorides of 3-{2-[(2/4-fluorophenoxy)-ethylamino]}-2-hydroxypropyl-4-alkoxybenzoates and four hydrochlorides of 3-tert-butylamino-2-hydroxypropyl-4-butoxybenzoates were prepared as potential antagonists of the β1-adrenergic receptor (beta-blockers). A multistep synthesis of these compounds is described as well as their detailed analytical characterization. The pharmacokinetic properties of these weak base compounds are significantly influenced by their acid-base dissociation constant, pK a. The knowledge of this value is crucial for new drug development. This paper is aimed at developing a methodology that utilizes pH-dependent 1H NMR spectroscopy for its routine analysis. The selected predicted physico-chemical parameters of the new (arylcarbonyloxy)aminopropanols (i.e., aryloxyaminopropanol derivatives) were compared with the model drugs esmolol and flestolol.

scholarly journals Determination of folic acid by capillary zone electrophoresis with indirect chemiluminescence detection

RSC Advances ◽  
2021 ◽  
Vol 11 (33) ◽  
pp. 20063-20069
Author(s):  
Tangjuan Zhao ◽  
Huaping Lin ◽  
Nan Li ◽  
Hongmei Shi ◽  
Weijun Kang ◽  
...  
Keyword(s):  
Capillary Electrophoresis ◽  
Folic Acid ◽  
Capillary Zone Electrophoresis ◽  
Chemiluminescence Detection ◽  
Capillary Electrophoresis Method ◽  
Zone Electrophoresis ◽  
Electrophoresis Method ◽  
On Line ◽  
Capillary Zone

A capillary electrophoresis method with on-line inhibited chemiluminescence detection was first used to determine folic acid.

scholarly journals Physicochemical Compatibility Investigation of Mesalazine and Folic Acid Using Chromatographic and Thermoanalytical Techniques

2020 ◽  
Vol 13 (8) ◽  
pp. 187
Author(s):  
Mario-Livio Jeličić ◽  
Edvin Brusač ◽  
Daniela Amidžić Klarić ◽  
Biljana Nigović ◽  
Sabina Keser ◽  
...  
Keyword(s):  
Folic Acid ◽  
Inflammatory Bowel Diseases ◽  
Hplc Method ◽  
Fixed Dose ◽  
Forced Degradation ◽  
Physicochemical Interaction ◽  
Scanning Calorimetry ◽  
Vitamin B9 ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel disease is a common name for Crohn’s disease and ulcerative colitis. These inflammatory states cause damage in the sidewalls of the gastrointestinal tract, resulting in malabsorption of food and vitamins. Folic acid (Vitamin B9) is often associated with inflammatory bowel diseases since reduced overall folate concentration in the human body may lead to the development of colorectal cancer and megaloblastic anaemia. However, its deficiency is easily compensated by taking an additional folic acid pill during regular therapy. At the moment, there are no studies that have examined the compatibility of folic acid with 5-aminosalicylate drugs used in the treatment of inflammatory bowel diseases. In this work, differential scanning calorimetry, forced degradation studies, isothermal stress testing and dissolution stability testing were used to determine the stability of folic acid and one of the most commonly used 5-aminosalicylates, mesalazine, when present in the same solution or blend. To monitor the assay of folic acid, mesalazine and nine of its related impurities, a single HPLC method was developed. Results of compatibility studies showed that no physicochemical interaction between mesalazine and folic acid occurs when combined, opening the path to the development of new formulations, such as a mesalazine/folic acid fixed-dose combination.

scholarly journals A Comprehensive Approach to Compatibility Testing Using Chromatographic, Thermal and Spectroscopic Techniques: Evaluation of Potential for a Monolayer Fixed-Dose Combination of 6-Mercaptopurine and Folic Acid

2021 ◽  
Vol 14 (3) ◽  
pp. 274
Author(s):  
Edvin Brusač ◽  
Mario-Livio Jeličić ◽  
Matija Cvetnić ◽  
Daniela Amidžić Klarić ◽  
Biljana Nigović ◽  
...  
Keyword(s):  
Folic Acid ◽  
Development Strategy ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Forced Degradation ◽  
Spectroscopic Techniques ◽  
Scanning Calorimetry ◽  
Forced Degradation Studies ◽  
Dose Combination ◽  
Inflammatory Bowel

In this work, a systematical compatibility investigation of 6-mercaptopurine and folic acid, two commonly used medications in the treatment of inflammatory bowel disease, for the needs of a fixed-dose combination development strategy is shown. Various techniques and approaches, such as differential scanning calorimetry, isothermal stress testing, attenuated total reflectance–Fourier-transform infrared spectroscopy, dissolution medium stability and forced degradation studies, were used to elucidate the possible interactions from different aspects. The results predominantly point to the absence of physicochemical interactions between the examined substances in a variety of possible conditions. However, the forced degradation of the blend of substances and excipients in basic conditions showed a drastic degradation of 6-mercaptopurine, signifying that attention needs to be directed to the careful selection of the excipients for the formulation. To sum up, our findings indicate that a fixed-dose combination of 6-mercaptopurine and folic acid could be produced using one formulation blend, immensely simplifying its manufacture.

Fast calibration of CBED patterns for quantitative analysis

1993 ◽  
Vol 51 ◽  
pp. 674-675
Author(s):  
M.A. Gribelyuk ◽  
M. Rühle
Keyword(s):  
Reciprocal Lattice ◽  
Accurate Determination ◽  
Incident Beam ◽  
Crystal Thickness ◽  
Structure Model ◽  
Beam Direction ◽  
Transmitted Beam ◽  
Reciprocal Vector ◽  
On Line

A new method is suggested for the accurate determination of the incident beam direction K, crystal thickness t and the coordinates of the basic reciprocal lattice vectors V1 and V2 (Fig. 1) of the ZOLZ plans in pixels of the digitized 2-D CBED pattern. For a given structure model and some estimated values Vest and Kest of some point O in the CBED pattern a set of line scans AkBk is chosen so that all the scans are located within CBED disks.The points on line scans AkBk are conjugate to those on A0B0 since they are shifted by the reciprocal vector gk with respect to each other. As many conjugate scans are considered as CBED disks fall into the energy filtered region of the experimental pattern. Electron intensities of the transmitted beam I0 and diffracted beams Igk for all points on conjugate scans are found as a function of crystal thickness t on the basis of the full dynamical calculation.

A panel of mono- and dinucleotide microsatellite markers is required for reliable determination of the MSI status in colorectal cancer

2001 ◽  
Vol 120 (5) ◽  
pp. A599-A599
Author(s):  
C ARNOLD ◽  
A GOEL ◽  
J CARETHERS ◽  
L WASSERMAN ◽  
C COMPTON ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Markers ◽  
Reliable Determination
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