RP-HPLC method validation for fast extraction and quantification of Levonorgestrel drug from silicone based intrauterine device intended for in-process and finished formulation

• Published in: Daru Vol. 29; no. 1; pp. 185 - 193
• Main Authors: Veeran, Midhu George, C., Karthikeyan, B., Bharaniraja, Painuly, Diksha, Aprem, Abi Santhosh
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2021; BioMed Central Ltd; Springer Nature B.V
• Subjects: Acetonitrile; Analysis; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid - methods; Chromatography, Reverse-Phase - methods; Contraceptive Agents, Female - analysis; Contraceptive Agents, Female - chemistry; Contraceptive drug implants; Detectors; High performance liquid chromatography; Intrauterine Devices; IUD; Levonorgestrel; Levonorgestrel - analysis; Levonorgestrel - chemistry; Liquefied natural gas; Medicinal Chemistry; Methods; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Reproducibility of Results; Research Article; Silicones; Silicones - chemistry; India; Validation; Levonorgestrel; Silicone; Intrauterine device; Quality by design (QbD)
• ISSN: 2008-2231; 1560-8115; 2008-2231
• DOI: 10.1007/s40199-021-00396-7

Background
To develop and validate a simple and consistent reversed phase high performance liquid chromatography (RP-HPLC) method for the estimation of Levonorgestrel (LNG) drug from silicone based intrauterine device.
Methods
Sample solution was prepared using tetrahydrofuran (THF) as solvent for the drug extraction, and RP-HPLC analysis was performed using Luna C18 analytical column (150 × 4.6 mm, 5 μm, 100 Å – Phenomenex), with a mobile phase consisting of a mixture of acetonitrile and water (50:50,
v
/v) at a flow rate of 1.0 ml/min and injection volume of 20 μl. Detection was carried out at 241 nm in PDA detector, with a total run time of 15 min. The method was validated in accordance with ICH guidelines. Method applicability was tested for optimizing formulation using quality-by-design approach, to check the stability and content uniformity of levonorgestrel-silicone mixture (core blend), and quantifying the amount of LNG from commercially available silicone based formulation.
Results
The retention time for LNG drug was obtained at 8.5 min (± 0.3 min). A linear relationship was observed over the concentration range of 2.6–15.6 μg/ml with the correlation coefficient (r) value 0.9999. The method was found to be precise within the acceptable limit (RSD < 2%) and the drug recovery from the intrauterine device was found in the range 99.78–100.0%. Content uniformity for different prototypes developed was observed in the range of 91.6–101.4%, and assay of optimized core blend was in the range of 97.78–106.79% during the 10 days of retention period for stability studies.
Conclusion
The validated method is found to be a simple, accurate, precise, reproducible, and hence can be used for the routine analysis of LNG such as in-process, quality control and stability assays of silicone based intrauterine devices by RP-HPLC.
Graphical abstract