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Current Analytical Chemistry

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ISSN (Print): 1573-4110
ISSN (Online): 1875-6727

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Research Article

Development and Validation of HPLC-UV Method for the Determination of Levothyroxine in Orodispersible Minitablets for Pediatric Application

Author(s): Olivera Camila Belen, Henestrosa Cecilia*, Favier Silvina, Dobrecky Cecilia, Flor Sabrina and Lucangioli Silvia*

Volume 20, Issue 7, 2024

Published on: 15 April, 2024

Page: [526 - 531] Pages: 6

DOI: 10.2174/1573411019666230823094439

Price: $65

Abstract

Background: Thyroid hormones play an important role in cognition and brain development. The determination of the content of levothyroxine, as well as related substances and dissolution test analysis, should be carried out by methods that are selective and highly sensitive due to the low concentration used in low dose orodispersible minitablets.

Objectives: This study aims to develop and validate an analytical method by HPLC-UV for the quantification of levothyroxine and its related substances in pharmaceutical formulations; looking forward to being this method suitable for a future dissolution test analysis using tandem mass spectrometry detector.

Methods: A Hypersil GOLD C18 (100 x 2.1 mm, 3 μm) column was used with 25°C column temperature, 5 μL injection volume, 0.3 mL/min flow rate and detection at 225 nm. The mobile phase consisted of methanol: 0.05% formic acid (55:45). The developed method was validated for specificity, linearity, precision, accuracy and robustness.

Results: The method is linear within the range of 2-20 μg mL-1 (R2=0.9982), which makes the method suitable for the evaluation of levothyroxine in pharmaceuticals formulations. LOQ was 0.17 μg/mL (0.85 ng on column) and LOD 0.05 μg/mL (0.25 ng on column) of LT4. Therefore, in terms of efficiency (1671), retention factor, k (6.79), Tailing factor, T (1.09) and resolution, Rs (5.11) the chromatographic method was found to be suitable according to USP 43.

Conclusion: The HPLC UV method was found to be linear, specific, precise, accurate and robust, therefore it is suitable for the quality control of levothyroxine in pharmaceutical ODMTs.

« Previous
[1]
Braverman, L.E.; Cooper, D.S., Eds.; Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text (Werner and Ingbars the Thyroid), 10th ed; Lippincott Williams & Wilkins: Philadelphia, 2013.
[2]
Razvi, S.; Weaver, J.U.; Pearce, S.H. Subclinical thyroid disorders: Significance and clinical impact. J. Clin. Pathol., 2010, 63(5), 379-386.
[http://dx.doi.org/10.1136/jcp.2008.057414] [PMID: 20418229]
[3]
Kim, D.W.; Park, J.W.; Willingham, M.C.; Cheng, S.Y. A histone deacetylase inhibitor improves hypothyroidism caused by a TRα1 mutant. Hum. Mol. Genet., 2014, 23(10), 2651-2664.
[http://dx.doi.org/10.1093/hmg/ddt660] [PMID: 24381310]
[4]
Vella, K.R.; Hollenberg, A.N. The actions of thyroid hormone signaling in the nucleus. Mol. Cell. Endocrinol., 2017, 458, 127-135.
[5]
Ares Segura, S.; Casano-Sancho, P.; Guindulain, M. Assessment of thyroid function in the preterm and/or very low birth weight newborn. An Pediatr (Engl Ed)., 2021, 95(4), 277.e1-277.e8.
[6]
Bernal, J. Thyroid hormones and brain development. Vitam. Horm., 2005, 71, 95-122.
[7]
Michael, C.W.; Kameyama, K.; Kitagawa, W.; Azar, N. Rapid on-site evaluation (ROSE) for fine needle aspiration of thyroid: Benefits, challenges and innovative solutions. Gland Surg., 2020, 9(5), 1708-1715.
[http://dx.doi.org/10.21037/gs-2019-catp-23] [PMID: 33224848]
[8]
Jonklaas, J.; Bianco, A.C.; Bauer, A.J.; Burman, K.D.; Cappola, A.R.; Celi, F.S.; Cooper, D.S.; Kim, B.W.; Peeters, R.P.; Rosenthal, M.S.; Sawka, A.M. Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid, 2014, 24(12), 1670-1751.
[http://dx.doi.org/10.1089/thy.2014.0028] [PMID: 25266247]
[9]
Hennessey, J.V. The emergence of levothyroxine as a treatment for hypothyroidism. Endocrine, 2017, 55(1), 6-18.
[PMID: 27981511]
[10]
Virili, C.; Antonelli, A.; Santaguida, M.G.; Benvenga, S.; Centanni, M. Gastrointestinal malabsorption of thyroxine. Endocr. Rev., 2019, 40(1), 118-136.
[PMID: 30476027]
[11]
WHO. WHO model formulary for children 2010. 2010. Available From: https://apps.who.int/iris/handle/10665/44309
[12]
Stoltenberg, I.; Breitkreutz, J. Orally disintegrating mini-tablets (ODMTs)--a novel solid oral dosage form for paediatric use. Eur. J. Pharm. Biopharm., 2011, 78(3), 462-469.
[http://dx.doi.org/10.1016/j.ejpb.2011.02.005] [PMID: 21324357]
[13]
Comoglu, T.; Ozyilmaz, E. Orally disintegrating tablets and orally disintegrating mini tablets - novel dosage forms for pediatric use. Pharm. Dev. Technol., 2019, 24(7), 902-914.
[http://dx.doi.org/10.1080/10837450.2019.1615090] [PMID: 31215850]
[14]
Tumuluri, V. Pharmaceutical mini-tabletsDrug Delivery Trends; Elsevier: Canada, 2020, pp. 123-139.
[15]
Thabet, Y.; Klingmann, V.; Breitkreutz, J. Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics. J. Clin. Pharmacol., 2018, 58(S10), S26-S35.
[16]
Shah, R.B.; Bryant, A.; Collier, J.; Habib, M.J.; Khan, M.A. Stability indicating validated HPLC method for quantification of levothyroxine with eight degradation peaks in the presence of excipients. Int. J. Pharm., 2008, 360(1-2), 77-82.
[http://dx.doi.org/10.1016/j.ijpharm.2008.04.018] [PMID: 18524511]
[17]
Takahashi, M.; Nagashima, M.; Shigeoka, S.; Kamimura, H.; Kamata, K. Determination of thyroid hormones in pharmaceutical preparations, after derivatization with 9-anthroylnitrile, by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. A, 2002, 958(1-2), 299-303.
[http://dx.doi.org/10.1016/s0021-9673(02)00367-9] [PMID: 12134828]
[18]
Smith, D.J.; Biesemeyer, M.; Yaciw, C. The separation and determination of liothyronine and levothyroxine in tablets by reversed-phase high performance liquid chromatography. J. Chromatogr. Sci., 1981, 19(2), 72-78.
[PMID: 7228964]
[19]
Garnick, R.L.; Burt, G.F.; Long, D.A.; Bastian, J.W.; Aldred, J.P. High-performance liquid chromatographic assay for sodium levothyroxine in tablet formulations: Content uniformity applications. J. Pharm. Sci., 1984, 73(1), 75-77.
[PMID: 6694088]
[20]
Rozing, G.; Nägele, E.; Hörth, P.; Vollmer, M.; Moritz, R.; Glatz, B.; Gratzfeld-Hüsgen, A. Instrumentation for advanced microseparations in pharmaceutical analysis and proteomics. J. Biochem. Biophys. Methods, 2004, 60(3), 233-263.
[PMID: 15345294]
[21]
The United States Pharmacopoeial Convention The United States pharmacopoeia: The national formulary; The United States Pharmacopoeial Convention Inc.: Rockville, 2020.
[22]
Collier, J.W.; Shah, R.B.; Bryant, A.R.; Habib, M.J.; Khan, M.A.; Faustinob, P.J. Development and application of a validated HPLC method for the analysis of dissolution samples of levothyroxine sodium drug products. J. Pharm. Biomed. Anal., 2011, 54(3), 433-438.

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