The competencies of four greenness assessment tools were tested. AGREE is the best greenness tool while NEMI is the poorest one. AGREE, GAPI, and ESA are reliable greenness tools.
A gradient elution high‐performance liquid chromatographic method with a diode array detector is introduced for the first time for the simultaneous estimation of three drugs, namely, oxytetracycline hydrochloride (OXT), lidocaine (LDC), and bromhexine hydrochloride (BRH), in a veterinary formulation (OxyClear® solution) that contains many interfering additives. The method used a C‐8 column. The chromatographic eluting solution included acidified water (0.1% trifluoroacetic acid in water) and acetonitrile at a 1‐ml/min flow rate and 254 nm as a nominated detection wavelength. The chromatographic process was assessed in terms of linearity, precision, accuracy, LOD, and LOQ. OXT, LDC, and BRH were linear in the range of 1–60, 5–100, and 1–60 μg/ml, respectively. The three drugs were determined successfully without the interference of three excipients having UV absorbances. Furthermore, the purities of the peaks of the three drugs were confirmed by comparing the UV spectra of investigated peaks to the UV reference spectra in Clarke's Analysis of Drugs and Poisons. The greenness value of the method was 0.69 with a faint green‐colored pictogram using the AGREE tool. These merits recommend the application of the planned method in QC laboratories for purity testing and concentration assays for the pure drugs and commercial formulations.
Background
Diflunisal (DIF) has analgesic and anti-inflammatory activity. It is a pharmacopeial drug found in the British Pharmacopoeia, and its major pharmacopeial impurity is biphenyl-4-ol (BPL).
Objective
Diflunisal was not determined before together with BPL. Presence of BPL could significantly affect the dose of DIF in its dosage forms; hence it is crucial to determine DIF and BPL in presence of each other.
Methods
Thin layer chromatography (TLC) is the first proposed method, where DIF and BPL are separated on silica gel TLC F254 plates. The eluent is toluene–acetone–acetic acid solution (3.5:6.5:1 by volume). Reversed-phase high-performance liquid chromatography (RP-HPLC) is the second suggested method, where mixture of DIF and BPL are separated on C18 (5 µm ps, 250 mm and 4.6 id) column using phosphate buffer pH = 4 (0.05M)–acetonitrile (40:60, v/v). Detection was done at 254 nm in both methods.
Results
For TLC method, a concentration range of 0.5–3 and 0.3–1.7 µg/band were used, with mean percentage recoveries 100.22% (SD 0.893) and 100.52% (SD 0.952) for DIF and BPL, respectively. RP-HPLC method was carried out over a concentration range of 5–30 and 2–9 μg/mL, with mean percentage recoveries 100.10% (SD 1.259) and 98.88% (SD 0.822) for DIF and BPL, respectively.
Conclusion
TLC and RP-HPLC methods were successfully applied for determination of DIF and BPL, quantitatively, whether in bulk powder or in pharmaceutical formulations.
Highlights
Two chromatographic methods were developed and validated according to ICH guidelines for assay of DIF and its pharmacopeial impurity.
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