PHARMACOKINETIC PROFILE OF METFORMIN HYDROCHLORIDE IN DRIED BLOOD SPOT OF HEALTHY SUBJECTS USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHYâ€“PHOTODIODE ARRAY
Objective: This study aimed to analyze the metformin hydrochloride in dried blood spot (DBS) sample and evaluate a pharmacokinetic profile in six
healthy subjects who administered 850-mg metformin hydrochloride in tablet using high-performance liquid chromatographyâ€“photodiode array
Methods: Metformin analysis was performed on data of six healthy subjects who administered 850 mg of metformin hydrochloride as tablets. Blood
samples were taken at 12-time points at intervals of up to 12 h, and data were analyzed using HPLCâ€“PDA.
Results: A linear calibration curve was obtained in the range of 25â€“5000 ng/mL, with r=0.9990. Pharmacokinetic profiles of metformin were obtained
using DBS samples from six healthy participants, with a Cmax of 347.3â€“416.22 ng/mL. The average tmax and t1/2 were obtained at 3 and 2 h, respectively,
and the area under the curve (AUC)0-t/AUC0-âˆž ratio was >80% for all subjects.
Conclusion: The DBS biosampling technique can be developed for application in pharmacokinetic study of metformin HCl.
a Pathophysiologic Approach. 9th ed. United States: The McGraw-Hill
Companies, Inc.; 2015.
2. Muchid A. Pharmaceutical Care for Diabetes Mellitus. Jakarta:
Indonesian Ministry of Health; 2005.
3. Aburuz S, Millership J, McElnay J. Dried blood spot liquid
chromatography assay for therapeutic drug monitoring of metformin.
J Chromatogr B Analyt Technol Biomed Life Sci 2006;832:202-7.
4. 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. Jakarta: Indonesian National Agency of
Food and Drug Control; 2011.
5. Tan MH, Alquraini H, Mizokami-Stout K, MacEachern M. Metformin:
From research to clinical practice. Endocrinol Metab Clin North Am
6. Earle RR, Bandaru KK, Lakshmi UA. Formulation and characterization
of sustained release coated matric granules of metformin hydrochloride.
Asian J Pharm Clin Res 2018;11:387-92.
7. Kotecha NC, Patel JK. Method development and validation of a
reversed-phase liquid chromatographic method for the simultaneous
estimation of selected anti diabetic drugs in the presence of their
degradation products. Asian J Pharm Clin Res 2018;11:345-52.
8. Bookya P, Raparla R, Sriamula HP, Tarrigopula S, Vanga S. Formulation
and evaluation of metformin hydrochloride sustained release oral
matrix tablets. Asian J Pharm Clin Res 2018;11:342-5.
9. Evans C, Arnold M, Bryan P, Duggan J, James CA, Li W, et al.
Implementing dried blood spot sampling for clinical pharmacokinetic
determinations: Considerations from the IQ consortium microsampling
working group. AAPS J 2015;17:292-300.
10. Center of Drug Evaluation and Research. Metformin Hydrochloride
Tablets. United States: Food and Drug Administration; 2002.
11. Scherf-Clavel M, HÃ¶gger P. Analysis of metformin, sitagliptin and
creatinine in human dried blood spots. J Chromatogr B Analyt Technol
Biomed Life Sci 2015;997:218-28.
12. Wilhelm AJ, den Burger JC, Swart EL. Therapeutic drug monitoring
by dried blood spot: Progress to date and future directions. Clin
13. Alshishani A, Makahleh A, Yap HF, Gubartallah EA, Salhimi SM, Saad B,
et al. Ion-pair vortex assisted liquid-liquid microextraction with back
extraction coupled with high performance liquid chromatography-UV for
the determination of metformin in plasma. Talanta 2016;161:398-404.
14. Evans G. A Handbook of Bioanalysis and Drug Metabolism. United
States of America: CRC Press; 2014.
15. Porta V, Schramm S, Kano E, Koono E, Armando Y, Fukuda K, et al.
HPLC-UV determination of metformin in human plasma for application
in pharmacokinetics and bioequivalence studies. J Pharm Biomed Anal
16. Sharma A, Jaiswal S, Shukla M, Lal J. Dried blood spots: Concepts,
present status, and future perspectives in bioanalysis. Drug Test Anal