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Synthetic painkillers, also known as synthetic analgesics, are chemically engineered compounds designed to alleviate pain. Unlike natural analgesics derived from plants (e.g., morphine from opium), synthetic painkillers are created through organic synthesis in pharmaceutical laboratories. These compounds play a crucial role in modern medicine, managing acute and chronic pain across a variety of clinical conditions.
1. Non - opioid analgesics:
Examples: Acetaminophen like paracetamol
NSAIDs like ibuprofen, diclofenac etc.,
2. Opioid Analgesics (Synthetic):
Examples: Fentanyl, Tramadol, Methadone, Oxycodone
3. Adjuvant Analgesics:
Used in combination for neuropathic pain (e.g., certain antidepressants or anticonvulsants with analgesic properties).
Screening of synthetic painkillers is critical to ensure purity, potency, efficacy, and safety. It involves both qualitative and quantitative analysis using advanced analytical techniques.
1. Fourier Transform Infrared Spectroscopy (FTIR):
Purpose: Identification of functional groups and confirmation of chemical structure. Rapid & non-destructive technique
Applications: Authentication of raw materials and detection of counterfeit drugs.
2. High-Performance Liquid Chromatography (HPLC):
Purpose: Quantitative analysis of active pharmaceutical ingredients (APIs), impurities, and degradation products. High resolution, reproducibility, and sensitivity.
Applications: Detection of drug purity, batch consistency, and stability testing.
3. Gas Chromatography-Mass Spectrometry (GC-MS):
Purpose: Identification and quantification of volatile and semi-volatile compounds. High sensitivity and specificity.
Applications: Screening of opioids and detecting trace levels of drug metabolites in biological samples (e.g., blood, urine). Purpose: Highly sensitive detection and quantification of compounds in complex matrices.
4. Liquid Chromatography–Mass Spectrometry (LC-MS/MS):
Purpose: Highly sensitive detection and quantification of compounds in complex matrices. Combines separation efficiency of LC with detection sensitivity of MS.
Applications: Bioanalytical testing, pharmacokinetics, and drug metabolism studies.
NSAID
Ibuprofen
Ketoprofen
Diclofenac
Aspirin
Paracetamol
Mefenamic acid
Naproxen
Betamethasone
Key functional groups present in Diclofenac drug:
| Functional Group | FTIR Characteristic Absorption Peaks (cm⁻¹) | Description |
|---|---|---|
| Carboxylic Acid (-COOH) | ~1700–1725 (C=O stretch) ~2500–3300 (O–H broad stretch) | Strong, broad absorption due to hydrogen bonding and carbonyl stretching |
| Aromatic Rings (C=C) | ~1450–1600 | Multiple medium-to-strong peaks from aromatic C=C stretching |
| Aromatic C–H | ~3000–3100 | Weak to medium absorption due to C–H stretching in the aromatic ring |
| Secondary Amine (-NH) | ~3300–3500 (N–H stretch) ~1500–1600 (N–H bend) | N–H stretching is sharp and medium, often observed around 3400 cm⁻¹ |
| C–Cl (Aryl chloride) | ~600–800 | Absorption due to C–Cl bond in dichlorophenyl rings |
Images obtained using the FTIR spectrum: Diclofenac standard:
Comparison studies on Standard Diclofenacand the sample:
HPLC:
| Functional Group | Characteristic FTIR Absorption (cm⁻¹) | Comments |
|---|---|---|
| Hydroxyl (-OH) (phenol) | ~3200–3550 (broad) | Broad peak due to hydrogen bonding; phenolic O–H stretch |
| Amide (-NHCO-) | ~3300–3500 (N–H stretch) ~1640–1690 (C=O stretch) ~1550–1650 (N–H bend) | N–H and C=O stretches indicate presence of secondary amide |
| Aromatic Ring (C=C) | ~1450–1600 | Multiple medium to strong peaks from aromatic C=C stretches |
| C–H (aromatic and aliphatic) | ~2800–3100 | Aromatic C–H appears slightly above 3000 cm⁻¹, aliphatic just below |
| C–N Stretch (Amide) | ~1230–1320 | Typically medium intensity; associated with amide group |
Key functional groups:
| Functional Group | Characteristic FTIR Absorption (cm⁻¹) | Comments |
|---|---|---|
| Carboxylic acid (-COOH) | ~1700–1725 (C=O stretch) ~2500–3300 (O–H broad stretch) | Strong, broad peak due to hydrogen-bonded O–H and sharp peak for carbonyl |
| Aromatic ring (C=C) | ~1450–1600 | Medium-to-strong peaks due to aromatic ring stretching |
| Alkyl C–H (sp³ C–H) | ~2850–2960 | C–H stretching from isobutyl and methyl groups | Aromatic C–H | ~3000–3100 | Weak to medium peak from aromatic C–H stretching |
| C–O (acid) | ~1200–1300 | C–O single bond from the –COOH group |
Comparison:
HPLC:
Key Functional groups
| Functional Group | Characteristic FTIR Absorption (cm⁻¹) | Comments |
|---|---|---|
| Hydroxyl (-OH) (alcohol) | ~3200–3600 (broad) | O–H stretching, broad due to hydrogen bonding (present at C11, C17, C21) |
| Ketone (C=O) (α,β-unsaturated and saturated) | ~1660–1750 | Strong peak for C=O stretch at C3 and C20 |
| Alkene (C=C) (conjugated) | ~1600–1680 | From the diene system (C1–C2, C4–C5) |
| Fluoro group (C–F) | ~1000–1400 | C–F stretch, often appears as a sharp, strong peak |
| Alkane C–H | ~2850–2960 | C–H stretching in aliphatic chains and methyl groups |
| C–O (alcohol) | ~1000–1300 | From secondary and tertiary alcohols |
Betamethasone standard:
Comparison:
Key functional groups:
| Wavenumber (cm⁻¹) | Functional Group |
|---|---|
| ~3400–3500 | O–H stretching (hydroxyl groups) |
| 2930–3055 | Aliphatic C–H stretching (–CH₂, –CH₃) |
| ~1712 | Carbonyl C=O stretching (C20 ketone) |
| ~1665 | Carbonyl C=O stretching (C3 ketone) |
| ~1620 | C=C stretching within the steroid ring system |
| 1430–1465 | C–H bending (ring deformation) |
| ~1130–1140 | C–O / C–O–C stretching (alcohol/ether linkages) |
| ~1055 | Additional C–O or P–O–C bands (in composites) |
HPLC:
Sample HPLC:
This sample shows no presence of dexamethasone active pharmaceutical ingredient.