Dimethyl Isosorbide: An Innovative Bio-Renewable Solvent for Sustainable Chromatographic Applications
Abstract
1. Introduction
2. Results and Discussion
2.1. Evaluation of DMI According to CHEM21 and SDS Lists
Property | DMI | H2O | EtOH | MeOH |
---|---|---|---|---|
Appearance | Clear, colorless liquid | Clear, colorless liquid | Clear, colorless liquid | Clear, colorless liquid |
Odor | No significant odor | No data available | Characteristic | Characteristic |
Odor threshold | No data available | No data available | No data available | No data available |
pH | No data available | 6.0–8.0 at 25 °C | 7.0 at 10 g/L at 20 °C | No data available |
Melting point/Freezing point | −84 °C | 0.0 °C | −114.0 °C | −97.8 °C |
Boiling point | 240 °C | 100.0 °C | 78.29 °C | 64.7 °C |
Flash point | 116 °C | Not applicable | 13 °C | 9.7 °C |
Viscosity | 6.62 mPa·s at 25 °C (range: 9.47 at 15 °C to 2.19 at 70 °C) [22] | No data available | 1.2 mPa·s at 20 °C | 0.544–<0.59 mPa·s at 25 °C |
Water solubility | 2000 g/L at 20 °C | Completely miscible | 1000 g/L at 20 °C | 1000 g/L at 20 °C |
Vapor pressure | 0.073000 mmHg (0.0973 hPa) at 25 °C. (est) [30] | No data available | 57.26 hPa at 19.6 °C | 169.27 hPa at 25 °C |
Vapor density | No data available | No data available | No data available | 1.11 |
Density | 1.166 g/cm3 at 20 °C | 1.000 g/cm3 at 3.98 °C | 0.79 g/cm3 at 20 °C | 0.79 g/cm3 at 20 °C |
Partition coefficient (log P) | −0.423 (est) [30] | −0.467 | −0.35 | −0.77 |
Autoignition temperature | 285 °C | No data available | 363–425 °C | 455.0 °C |
Decomposition temperature | No data available | No data available | Distillable at normal pressure | Distillable at normal pressure |
2.2. Investigation of Miscibility of DMI with Water
2.3. Investigation of the Viscosity of DMI and Its Mixtures with H2O and EtOH
2.4. Determination of the UV Cut-Off of DMI and Its Implications for Chromatographic Use
2.5. Determination of the Partition Coefficient (logP) of DMI
2.6. Investigation of the Chromatographic Behavior of DMI Using Central Composite Face 23 Experimental Design
2.7. Investigation of the Applicability of DMI as an Eluent in Chromatographic Analyses
3. Materials and Methods
3.1. Model Compounds and Reagents
3.2. Experimental Setup and Equipment Used
3.3. Selection Methodology
3.4. Miscibility Experiments
3.5. Viscosity Measurements
3.6. UV Cut-Off Determination
3.7. Partition Coefficient Determination
3.8. Design of Experiments (DoE) for Investigation of the Chromatographic Behavior of DMI
3.9. Conventional Method and Method Using DMI as an Eluent in the LC Mobile Phase for Determining Preservative Content in Carbocysteine, Loratadine, and Paracetamol Oral Solutions
3.10. Preparation of Standard Solutions and Test Solutions for the Determination of MPHB and PPHB in Oral Solutions
3.10.1. Carbocisteine Oral Solution 250 mg/5 mL
3.10.2. Paracetamol Oral Solution 120 mg/5 mL
3.10.3. Loratadine Oral Solution 1 mg/mL
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACN | Acetonitrile |
ACS | American Chemical Society |
As | Asymmetry Factor (Peak Symmetry) |
C18 | Octadecylsilane-bonded Stationary Phase |
CCF | Central Composite Face |
CHEM21 | Chemical 21st Century (Sustainable Chemistry Initiative) |
°C | Degrees Celsius |
DMI | Dimethyl Isosorbide |
DoE | Design of Experiments |
EP/Ph Eur | European Pharmacopoeia |
est | Estimated |
EtOH | Ethanol |
GAC | Green Analytical Chemistry |
GSK | GlaxoSmithKline |
H2O | Water |
HPLC | High-performance Liquid Chromatography |
ISO | International Organization for Standardization |
k′ | Retention Factor (Capacity Factor) |
L/mol·cm | Liters per Mole per Centimeter (Unit for Molar Absorption Coefficient) |
LC | Liquid Chromatography |
log P | Partition Coefficient (Logarithmic Scale) |
MeOH | Methanol |
mol/L | Moles per Liter (Concentration Unit) |
MPHB | Methylparahydroxybenzoate/Methylparaben |
mPa·s | Millipascal Second (Unit of Viscosity) |
N | Number of Theoretical Plates |
nm | Nanometers (Wavelength Unit) |
OECD | Organisation for Economic Co-operation and Development |
Pcolumn | Column Backpressure |
PPHB | Propylparahydroxybenzoate/Propylparaben |
RC | Regenerated Cellulose |
RP-HPLC | Reverse-Phase High-Performance Liquid Chromatography |
R | Correlation Coefficient |
RS | Reference Standard |
Rt | Retention Time |
SDS | Safety Data Sheet |
UV | Ultraviolet |
UHPLC | Ultra-High-Performance Liquid Chromatography |
v/v | Volume/Volume ratio |
VOC | Volatile Organic Compound |
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Parameter | DMI | DMC | Cyrene | MeOH | EtOH | Rating Scale |
---|---|---|---|---|---|---|
VOC Emissions | 10 | 5 | 10 | 3 | 4 | 1 = very high, 10 = very low |
Aquatic Impact | 9 | 9 | 9 | 10 | 9 | 1 = very high, 10 = very low |
Air Impact | 6 | 7 | 6 | 7 | 5 | 1 = very high, 10 = very low |
Health Hazard | 4 | 10 | 4 | 4 | 10 | 1 = very high, 10 = very low |
Exposure Potential | 9 | 6 | 8 | 6 | 8 | 1 = high, 10 = very low |
Flammability/Explosion Risk | 9 | 6 | 10 | 5 | 6 | 1 = very high, 10 = very safe |
Reactivity | 8 | 10 | 10 | 10 | 10 | 1 = highly reactive, 10 = stable |
Biotreatability | 5 | 5 | 5 | 3 | 3 | 1 = poor, 10 = excellent |
Recycle Potential | 4 | 3 | 4 | 4 | 5 | 1 = very low, 10 = high |
Incineration Suitability | 4 | 4 | 4 | 4 | 5 | 1 = poor, 10 = excellent |
Sample | Viscosity (mPa·s) at 25 °C (Mean ± SD, n = 3) | Viscosity (mPa·s) at 40 °C (Mean ± SD, n = 3) | Viscosity (mPa·s) at 60 °C (Mean ± SD, n = 3) |
---|---|---|---|
Pure DMI | 6.70 ± 0.10 | 4.53 ± 0.32 | 2.79 ± 0.03 |
70% DMI:30% H2O | 6.38 ± 0.08 | 3.84 ± 0.01 | 2.40 ± 0.23 |
50% DMI:50% H2O | 3.99 ± 0.11 | 2.73 ± 0.11 | 1.64 ± 0.01 |
30% DMI:70% H2O | 2.38 ± 0.01 | 1.68 ± 0.01 | 1.08 ± 0.02 |
Sample | Viscosity (mPa·s) at 25 °C (Mean ± SD, n = 3) | Viscosity (mPa·s) at 40 °C (Mean ± SD, n = 3) | Viscosity (mPa·s) at 60 °C (Mean ± SD, n = 3) |
---|---|---|---|
33.33% DMI:33.33% H2O: 33.33% EtOH | 2.31 ± 0.02 | 2.29 ± 0.02 | 1.49 ± 0.02 |
50% DMI:25% H2O: 25% EtOH | 2.51 ± 0.05 | 2.62 ± 0.10 | 1.76 ± 0.01 |
25% DMI:50% H2O: 25% EtOH | 1.88 ± 0.02 | 1.97 ± 0.08 | 1.29 ± 0.03 |
25% DMI:25% H2O: 50% EtOH | 2.01 ± 0.02 | 2.01 ± 0.01 | 1.28 ± 0.01 |
Exp. Name | Experimental Factors | Responses | ||||
---|---|---|---|---|---|---|
DMI % (v/v) | EtOH % (v/v) | Temperature (°C) | Viscosity (mPa·s) | k′ | Pcolumn (Bar) | |
N1 | 25 | 5 | 40 | 1.629 | 7.6 | 200 |
N2 | 45 | 5 | 40 | 2.632 | 4.6 | 286 |
N3 | 25 | 25 | 40 | 1.98 | 3.9 | 277 |
N4 | 45 | 25 | 40 | 2.564 | 0.7 | 304 |
N5 | 25 | 5 | 60 | 1.242 | 13.7 | 164 |
N6 | 45 | 5 | 60 | 1.656 | 3.4 | 262 |
N7 | 25 | 25 | 60 | 1.264 | 2.7 | 210 |
N8 | 45 | 25 | 60 | 1.621 | 0.6 | 281 |
N9 | 25 | 15 | 50 | 1.509 | 8.1 | 217 |
N10 | 45 | 15 | 50 | 2.027 | 1.6 | 233 |
N11 | 35 | 5 | 50 | 1.627 | 8.4 | 221 |
N12 | 35 | 25 | 50 | 1.862 | 1.5 | 276 |
N13 | 35 | 15 | 40 | 2.241 | 4.4 | 210 |
N14 | 35 | 15 | 60 | 1.465 | 3.2 | 226 |
N15 | 35 | 15 | 50 | 1.805 | 3.6 | 261 |
N16 | 35 | 15 | 50 | 1.797 | 3.6 | 261 |
N17 | 35 | 15 | 50 | 1.786 | 3.6 | 260 |
Chromatographic Parameter | CarbocysteineOral Solution 250 mg/5 mL | Loratadine Oral Solution 1 mg/mL | Paracetamol Oral Solution 120 mg/5 mL | |||
---|---|---|---|---|---|---|
Conventional Method * | Method with DMI ** | Conventional Method * | Method with DMI ** | Conventional Method * | Method with DMI ** | |
Rt MPHB (min) | 4.54 | 5.45 | 3.76 | 5.41 | 3.21 | 5.35 |
As MPHB (EP) | 0.95 | 0.97 | 0.95 | 0.99 | 1.12 | 0.99 |
N MPHB (EP) | 6834 | 8561 | 6834 | 8467 | 5256 | 7704 |
k′ MPHB | 2.78 | 3.19 | 1.89 | 3.16 | 2.21 | 3.11 |
Rt PPHB (min) | / | / | 6.80 | 15.90 | 7.32 | 15.54 |
As PPHB (EP) | / | / | 0.90 | 0.95 | 1.10 | 0.96 |
N PPHB (EP) | / | / | 6591 | 8202 | 5276 | 7511 |
k′ PPHB | / | / | 4.23 | 11.23 | 6.30 | 10.96 |
Pcolumn (bar) | 234 | 191 | 198 | 192 | 356 | 198 |
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Damjanoska, A.; Mitreska, K.; Petrova, M.; Acevska, J.; Brezovska, K.; Nakov, N. Dimethyl Isosorbide: An Innovative Bio-Renewable Solvent for Sustainable Chromatographic Applications. Molecules 2025, 30, 2713. https://doi.org/10.3390/molecules30132713
Damjanoska A, Mitreska K, Petrova M, Acevska J, Brezovska K, Nakov N. Dimethyl Isosorbide: An Innovative Bio-Renewable Solvent for Sustainable Chromatographic Applications. Molecules. 2025; 30(13):2713. https://doi.org/10.3390/molecules30132713
Chicago/Turabian StyleDamjanoska, Aleksandra, Kristina Mitreska, Matilda Petrova, Jelena Acevska, Katerina Brezovska, and Natalija Nakov. 2025. "Dimethyl Isosorbide: An Innovative Bio-Renewable Solvent for Sustainable Chromatographic Applications" Molecules 30, no. 13: 2713. https://doi.org/10.3390/molecules30132713
APA StyleDamjanoska, A., Mitreska, K., Petrova, M., Acevska, J., Brezovska, K., & Nakov, N. (2025). Dimethyl Isosorbide: An Innovative Bio-Renewable Solvent for Sustainable Chromatographic Applications. Molecules, 30(13), 2713. https://doi.org/10.3390/molecules30132713