INCURRED SAMPLE STABILITY OF METFORMIN HYDROCHLORIDE IN PLASMA OF SIX HEALTHY SUBJECTS USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
Objective: This study aimed to measure metformin levels and evaluates the incurred stability in plasma of six healthy subjects after administration
850 mg metformin hydrochloride tablet using high-performance liquid chromatography.
Methods: Samples were collected from six healthy subjects who were administered 850 mg metformin hydrochloride tablet. Blood was collected from
the subjects at up to 12-time points throughout a 12 h period. Sample stability was analyzed on days 7, 14, and 30. The analysis was conducted using
C-18 columns, a column temperature of 40Â°C, a mobile phase consisting of acetonitrile-phosphate buffer (pH 7.0; 40:60 v/v), a flow rate of 1 mL/min,
the photodiode array detector set at a wavelength of 234 nm, and calcium atorvastatin as the internal standard.
Results: All metformin HCl samples collected on days 7, 14, and 30 from subjects 1 to 6 met stability requirement based on the European Medicines
Agency Bioanalytical Guideline (2011), which state that the percentage difference value not >20%. In addition, the developed method for analyzing
metformin HCl in plasma was linear in the concentration range of 20.0â€“5000.0 ng/mL (r=0.9999).
Conclusion: The incurred sample of metformin hydrochloride in plasma of six healthy subjects was stable until 30 days after drug administration.
2. DiPiro JT, Talbert RL, Yee G, Matzke G, Wells B, Posey LM.
Pharmacotherapy. A Pathophysiologic Approach. 7th ed. United States
of America: McGraw-Hill; 2008.
3. Diwedi R, Alexandar S, Chandrasekar MJ. Preparation and in vitro
evaluation of sustained release tablet formulations of metformin HCL.
Asian J Pharm Clin Res 2012;5:45-8.
4. Ingle PV, Talele GS. Adverse effects of metformin in combination
with glimepiride and glibenclamide in patients with Type 2 diabetes
mellitus. Asian J Pharm Clin Res 2012;5:108-10.
5. Indonesian National Agency of Food and Drug Control. Regulation
from Head of No. HK.03.1.23.12.11.10217 about Drug Obligate
Equivalence Study Jakarta; 2011.
6. Rout SP, Kar DM, Mohapatra SB, Swain SP. Anti-hyperglycemic effect
Annova reticulata L. Leaves on experimental diabetic rat model. Asian
J Pharm Clin Res 2013;6:56-60.
7. European Medicines Agency. Guideline on Bioanalytical Method
Validation. Vol. 44. London: An Agency of the European Union; 2011.
8. Food and Drug Administration. Guidance for Industry Bioanalytical
Method Validation. United States of America: Department of Health
and Human Services; 2015.
9. Lowes S, LeLacheur R, Shoup R, Garofolo F, Dumont I, Martinez S,
et al. Recommendations on incurred sample stability (ISS) by GCC.
10. Aburuz S, Millership J, McElnay J. Dried blood spot liquid
chromatography assay for the therapeutic drug monitoring of
metformin. J Chromatogr B Analyt Technol Biomed Life Sci