Ten different levothyroxine products manufactured by six companies were analyzed by high-performance liquid chromatography. Although nine products met the United States Pharmacopeia requirements, one product was found to have only 47% of expected potency. Until these products become more uniform, we would not recommend interchangeability of levothyroxine preparations

Stoffer, Sheldon S.

Szpunar, Walter E.

English

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 36 Number 1 Article 17 3-1988 Potency of Current Levothyroxine Preparations Evaluated by High-Performance Liquid Chromatography Sheldon S. Stoffer Walter E. Szpunar Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Stoffer, Sheldon S. and Szpunar, Walter E. (1988) "Potency of Current Levothyroxine Preparations Evaluated by High-Performance Liquid Chromatography," Henry Ford Hospital Medical Journal : Vol. 36 : No. 1 , 64-65. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol36/iss1/17 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Clinical Note Potency of Current Levothyroxine Preparations Evaluated by High-Performance Liquid Chromatography Sheldon S. Stoffer, MD,* and Walter E. Szpunar, PhD* Ten different levothyroxine products manufactured by six companies were analyzed by high-performance liquid chromatography. Although nine products met the United States Pharmacopeia requirements, one product was found to have only 47% of expected potency. Until these products become more uniform, we would not recommend interchangeability of levothyroxine preparations. (Henry Ford Hosp MedJ 1988;36:64-5) In 1980 we demonsttated that the mean thyroxine content can be different in generic tablets when compared to that of brand name products. In addition, we demonstrated that a brand name prod-uct (Synthroid®) had only 78% of expected potency (1). Since then, the United States Pharmacopeia (USP) requirements have been modified so that manufacturers must evaluate levothyrox-ine content by high-performance liquid chromatography (HPLC) (2). In 1984 we reported that Synthroid® had been refor-mulated and had 100% of expected potency (3). We reassessed the content of a number of manufacturers' products using HPLC to determine if these products are currently more uniform. Materials and Methods Ten different levothyroxine products manufactured by six companies were analyzed by HPLC (Applied Analytical Labo-ratories, Wilmington, NC) (2). Local drugstores were contacted until ten different levothyroxine products were obtained. Between 17 and 21 tablets of each product were analyzed. The tablets were split into two groups, and each group was batch-analyzed separately. The analysis for each product was completed in one day, and all products were analyzed over a three-day period. Analysis of each extraction was duplicated. Since two batch extractions were done on each product, each group of tablets was assayed four times. The only exception was product 10, which was submitted twice and treated as two sepa-rate products. Therefore, product 10 was analyzed eight times. All tablets were 0.1 mg strength and were purchased in the fall of 1986. The assays were performed in June 1987. Results The results of our analyses are shown in the Table. Nine prod-ucts fell within the USP requirement of ± 10%, but product 10 had only 47% of expected potency. Table Thyroxine Content of 100 pg Tablets* Expiration % of Expected Date Product Manufacturer Contentt (month/year) 1 A 95 2/88 2 B >)4 1/88 3 C 95 3/88 4 c 96 5/88 5 c 102 12/87 6 D 91 10/88 7 c 9S 4/88 8 ll 96 1/89 9 F 100 10/87 10 C 47 f48t 145 7/87 *These levothyroxine products were distributed under ten different labels. tCoefficient of variation < 1.8%. tTwo separate submissions: coefficient of variation - 3.6% for combined analysis. Discussion A recent study by Dong et al (4) showed frequent non-equivalence of levothyroxine products by tablet HPLC analysis. However, these levothyroxine products were purchased in 1981, before the introduction of the HPLC requirement for manufac-turers. We suspect that the new USP HPLC requirement has im-proved the uniformity of levothyroxine products. However, Fish et al (5) recently reported that one generic product had only 34% of expected potency. Our data show that yet another company had at least one lot (product 10) with less than expected potency Submitted for publicadon: November 25. 1987. Accepted for publicauon; March 31. 1988, Formerly Departmeni of Internal Medicine, Henry Ford Hospital, Currenlly Oakland Internists, Southfield, tAssociated Endocrinologists, Southfield, Address correspondence to Dr Stoffer, Oakland Internists, 23077 Greenfield, Suite 205, Southfield. Ml 48075, 64 Henry Ford Hosp Med J—Vol 36, No 1, 1988 Currenl Levothyroxine Preparations—Staffer & Szpunar (47%). We admit that our study is limited. To better estimate the magnitude of the problem, a larger study evaluating different lots, different time periods, and different tablet strengths is needed. We hope this paper will stimulate investigators at re-search centers where such a study may be feasible. The Food and Dmg Administration currently does not recom-mend interchangeability of levothyroxine products (6). Nev-ertheless, generic levothyroxine products are available and are being interchanged for each other and for the brand name prod-ucts, at least in Michigan. The FDA's advice is not binding on the United States, and each state may allow interchangeability for the products that the FDA considers not interchangeable (6). We are concemed that levothyroxine products still show signifi-cant variability by HPUC (in vitro) testing. The USP has no re-quirement for bioavailability (in vivo) studies for levothyroxine products (7). Until levothyroxine products become more uni-form, we agree with the FDA's position that these products not be interchanged. We hope that levothyroxine products will con-tinue to be improved in the future. References 1, Stoffer SS, Szpunar WE, Potency of brand name and generic levothyroxine products, JAMA 1980;244:1704-5, 2, Garnick Rl. Burt GF, Borger FR. et al. In: Hormone drugs. Proceedings of the FDA USP workshop on drug and reference standards for insulins, somatropins, and thyroid-axis hormones, Rockville, IL: USP Convenfion, Inc, 1982:504-16, 3, Stoffer SS, Szpunar WE, Potency of levothyroxine products, JAMA 1984;251:635-6, 4, Dong BJ, Young VR. Rapoport B, The nonequivalence of levothyroxine products. Drug Intell Clin Pharm 1986:20:27, 5, Fish LH, Schwartz HL. Cavanaugh J. Steffes MW, Bantle JP, Oppenheimer JH, Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism: Role of triiodothyronine in pituitary feedback in humans, N Engl J Med 1987;316:764-70, 6, Proceedings of the Food and Drug Administration. Bioequivalence Hear-ing (September 29. 30. October 1), Washington, DC: J,W, Marriott, 1986:716, 7, Greenstadl MA, Spencer CA, Lum SMC, Kaptein EM, Nicoloff JT, Non-isotopic method for delermination of oral thyroxine absorption. In: Hormone drugs. Proceedings of the FDA USP workshop on drug and reference standards for insulins, ,somatropins, and thyroid-axis hormones, Rockville, IL: USP Con-vemion, Inc, 1982:534-9, Henry Ford Hosp Med J—Vol 36, No I . 1988 Current Levothyroxine Preparations—Stoffer & Szpunar 65 

Potency of Current Levothyroxine Preparations Evaluated by High-Performance Liquid Chromatography

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Potency of Current Levothyroxine Preparations Evaluated by High-Performance Liquid Chromatography

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