How quickly does T3 degrades in DMSO or Alcohol?

[master.on]

A few hours? A couple days? A week?

I will order an enclosed magnetic stirrer equipment to avoid the risk of breathing airborne T3 powder.

 

[master.on]

bump


We do not recommend storing the aqueous solutions for more than one day..
T3 (sodium salt) is soluble in organic solvents such as DMSO and dimethylformamide (DMF) which SOULD BE PURGED WITH AN INERT GAS
https://www.caymanchem.com/pdfs/16028.pdf
I guess purging is needed to get rid of dissolved Oxygen and water?


For how long is a solution of T3 (triiodo-L-thyronine) stable in DMSO?
While a solution of T4 in DMSO is stable for 24 hours, I cannot find any references for T3. Does anyone have an answer?
For how long is a solution of T3 (triiodo-L-thyronine) stable in DMSO?
While T3 is more stable than T4, 24 hours doesn't look good.
Especially bad since it is DMSO, not alcohol or water.


Abstract
Levothyroxine tablets, 50 microg, have been marketed for many decades but have had numerous recalls due to degradation and failure to meet potency. These experiments were devised to study the effects of various excipients on the stability of levothyroxine sodium pentahydrate in aqueous slurries and in formulated tablets. The active alone was found to be stable in the solid state for 6 months at 40 degrees C/75% RH whether stored in open or closed containers, and was found to be non-hygroscopic under normal processing conditions (>30% RH). In aqueous slurries with an excipient, the stability of the active improved as the pH of the slurry was increased from pH 3 to 11. Tablets manufactured with lactose anhydrous, starch, or microcrystalline cellulose failed to meet USP assay requirements at 3 months at 40 degrees C/75% RH. Tablets manufactured with dibasic calcium phosphate or mannitol met USP assay requirements at 3, but not 6 months when stored at 40 degrees C/75% RH. Tablets manufactured with dibasic calcium phosphate and a basic pH modifier, such as sodium carbonate, sodium bicarbonate, or magnesium oxide, met the USP assay requirements at both 3 and 6 months. Thus, the use of basic pH modifiers is a potential technique for improving the stability of levothyroxine sodium pentahydrate tablets.
The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets (PDF Download Available). Available from: The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets (PDF Download Available) [accessed Jul 14, 2017].
Again for T4 which is less stable than T3 but
we can learn that a basic pH modifier like Sodium carbonate/bicarbonate and dibasic Calcium phosphate are desirable in tabs.

 

[master.on]

It decomposes photochemically by both normal daylight and under irradiation to form several degradation products...
Liothyronine had similar sensitivity as thyroxine to irradiation and degraded to the same products...
To make sure that the high decomposition is only produced by light action, one of the sample solutions was protected from light with aluminum foil. After 2 days, no degradation products were detected in the protected sample...
Identification and quantitation of sodium-thyroxine and its degradation products by LC using electrochemical and MS detection (PDF Download Available)
So cool and dark temps are required when brewing



Abstract
The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C.
Stability of an extemporaneously compounded levothyroxine sodium oral liquid. Available from: Stability of an extemporaneously compounded levothyroxine sodium oral liquid
Again t4, so brewed T3 will probably need to be stored in the fridge

 

[master.on]

3,3′,5′-Triiodo-L-thyronine-13C6 solution
100 μg/mL in methanol with 0.1N NH3, ampule of 1 mL, certified reference material
3,3′,5′-Triiodo-L-thyronine-13C6 solution 100 μg/mL in methanol with 0.1N NH3, ampule of 1 mL, certified reference material | Sigma-Aldrich
While it's a radioactive labeled version, I don't think solubility/stability is much different from plain T3.
While it's likely pretty stable (despite being advised to store at -20 C), Methanol ain't something you can safely drink. Dissolved Ammonia makes it worse.

 

[master.on]

Kato and colleagues24 conducted stability studies for levothyroxine sodium and reported that storage away from light and under refrigeration produced a longer-lasting injection. Two IV formulations prepared by Cano and associates25 were stable over a period of 30 days. Samples of sodium levothyroxine in 0.01 N methanolic sodium hydroxide remained stable at 5°C over a 6- month period.
http://ibrarian.net/navon/paper/P_E_E_R_R_E_V_I_E_W.pdf?paperid=21980065
So it looks like Methanol makes it more stable than Ethanol does. Also an alkaline substance (in this one Sodium Hydroxide) is badly needed for stability.
While very small amounts of Methanol can still be ingested safely (probably less than 1 mL a day), the Sodium Hydroxide makes it too alkaline and may burn the tongue as it has a pH of about 12.

 

[master.on]

Mexican Cynomel was about the only T3 med that contains Ethyl alcohol:

CYNOMEL, a Mexican version of T3 only, a shortage started in 2016…

Corn Starch
Calcium Sulfate Dehydrate
Sugar glass
Talc
Sterate acid powder
Gelatin
Ethyl alcohol
Purified water
Armour vs. Other Brands (NDT, T3, etc) - Stop The Thyroid Madness

Obviously Cynomel tabs didn't feel damp
So either:
1 Very little Ethyl alcohol and water was added so it was absorbed by other ingredients
2 They waited for Ethyl alcohol and Water to evaporate
IMO #2 is more likely


STTM website mentions some other T3 meds containing alcohol

TRIOSTAT is an injection version of synthetic T3 (1), where each ml contains 10 mcg of liothyronine, as well as

alcohol, 6.8% by volume
anhydrous citric acid, 0.175 mg
ammonia, 2.19 mg, as ammonium hydroxide


LIOTIR, a liquid form of Liothyronine and is taken in drops. Said to contain alcohol. (Patients have expressed fear of accuracy if it’s just based on drops.)

 

[master.on]

Mexican Cynomel was recalled in Spain
https://www.aemps.gob.es/informa/alertas/medicamentosUsoHumano/2014/docs/calidad_07-2014-cynomel.pdf

According to Google translate the reason was
Description of defect:
Detection of an out-of-specification result in stability studies
Google Translate

I wonder if Cynomel was intentionally OVERdosed, reason why it felt much more potent than other T3 meds.


Page 1
PHARMACEUTICAL ALERT Reference: DICM / CONT / MJA Alert Nº: R_07 / 2014 Date: February 11, 2014 Product: Foreign medicine Trademark and presentation: CYNOMEL 25 micrograms 30 tablets DCI or DOE: SODIUM LYIOTIRONINE Lots: 1390, 1391 and 1392 Date of Expiry: 6/30/2014 Responsible in Spain of the medicine: PHARMA INTERNATIONAL, SA Laboratory Manufacturer: SANOFI AVENTIS (France) Address of the person responsible for the product: C / General Oráa, 70, 28006, Madrid Description of defect: Detection of an out-of-specification result in stability studies Distribution Information: See attached Classification of defects: Class 2 Precautionary measures taken: Withdrawal from the market of all units distributed in lots 1390, 1391 and 1392 and return to Laboratory by the usual channels Actions to be carried out by the CCAA: Follow-up of withdrawal HEAD OF DEPARTMENT INSPECTION AND CONTROL OF MEDICINES Belén Escribano Romero EMAIL page 1 of 2 C / CAMPEZO, 1 - EDIFICIO 8 28022 MADRID Sgicm@aemps.es Tel: 91 822 52 02 | Fax: 91 822 52 43
Page 2
MINISTRY OF HEALTH, SOCIAL SERVICES AND EQUALITY Page 2 of 2 Spanish Agency of Medications and Products Toilets, AEMPS Annexed FIRST NAME PLACE AUTONOMOUS COMMUNITY Ppli Córdoba (DS Guadalquivir) Cordova Andalusia Ppli Granada (H. Virgen Nieves) Pomegranate Ppli Granada (Dist. Metropolitano) Pomegranate Ppli Malaga (DSMalaga) Malaga Ppli Sevilla (Dist.S.Seeker-Quiñones) Seville Hospital Son Espases Palma Palma de Mallorca Balearics Ib Salut Ibiza Hospital Mateu Orfila Mahon Scs / Compl. H.Mat-Insular Las Palmas Canary Islands Hospital Marqués Valdecilla Santander Cantabria Provincial Health Office-C. Real Ciudad Real Castilla la Mancha Mancha Hospital Center Complex Alcazar of San Juan Serv.Perif.Consej.Sanidad Guadalajara Guadalajara Serv.Perif.Consej.Sanidad Toledo Toledo Gestion Hosp. 2000 (Sj Dios) Burgos Burgos Castile and Leon Health Management Areas of León Lion Area Health Management Segovia Segovia Direc. Territ. Saint. And B.Soc Segovia Segovia Health Management Areas of Valladolid Valladolid Hebron Valley General Hospital Barcelona Catalonia Hospital Santa Cruz and San Pablo Barcelona Hebron Valley Children's Hospital Barcelona C. Sanitari del Maresme Mataró University Hospital Arnau Vilanova Lérida San Juan Reus Municipal Hospital Reus Ses-G. Area Badajoz (At.Primaria) Badajoz Estremadura Health Area Management Llerena-Zafra Zafra Don Benito Health Area Management Don Benito


Original Spanish text:
Domicilio social del responsable del producto:
Contribute a better translation

 

[master.on]

Mexican Cynomel was recalled in Spain
https://www.aemps.gob.es/informa/alertas/medicamentosUsoHumano/2014/docs/calidad_07-2014-cynomel.pdf

According to Google translate the reason was
Description of defect:
Detection of an out-of-specification result in stability studies
Google Translate

I wonder if Cynomel was intentionally OVERdosed, reason why it felt much more potent than other T3 meds.


Page 1
PHARMACEUTICAL ALERT Reference: DICM / CONT / MJA Alert Nº: R_07 / 2014 Date: February 11, 2014 Product: Foreign medicine Trademark and presentation: CYNOMEL 25 micrograms 30 tablets DCI or DOE: SODIUM LYIOTIRONINE Lots: 1390, 1391 and 1392 Date of Expiry: 6/30/2014 Responsible in Spain of the medicine: PHARMA INTERNATIONAL, SA Laboratory Manufacturer: SANOFI AVENTIS (France) Address of the person responsible for the product: C / General Oráa, 70, 28006, Madrid Description of defect: Detection of an out-of-specification result in stability studies Distribution Information: See attached Classification of defects: Class 2 Precautionary measures taken: Withdrawal from the market of all units distributed in lots 1390, 1391 and 1392 and return to Laboratory by the usual channels Actions to be carried out by the CCAA: Follow-up of withdrawal HEAD OF DEPARTMENT INSPECTION AND CONTROL OF MEDICINES Belén Escribano Romero EMAIL page 1 of 2 C / CAMPEZO, 1 - EDIFICIO 8 28022 MADRID Sgicm@aemps.es Tel: 91 822 52 02 | Fax: 91 822 52 43
Page 2
MINISTRY OF HEALTH, SOCIAL SERVICES AND EQUALITY Page 2 of 2 Spanish Agency of Medications and Products Toilets, AEMPS Annexed FIRST NAME PLACE AUTONOMOUS COMMUNITY Ppli Córdoba (DS Guadalquivir) Cordova Andalusia Ppli Granada (H. Virgen Nieves) Pomegranate Ppli Granada (Dist. Metropolitano) Pomegranate Ppli Malaga (DSMalaga) Malaga Ppli Sevilla (Dist.S.Seeker-Quiñones) Seville Hospital Son Espases Palma Palma de Mallorca Balearics Ib Salut Ibiza Hospital Mateu Orfila Mahon Scs / Compl. H.Mat-Insular Las Palmas Canary Islands Hospital Marqués Valdecilla Santander Cantabria Provincial Health Office-C. Real Ciudad Real Castilla la Mancha Mancha Hospital Center Complex Alcazar of San Juan Serv.Perif.Consej.Sanidad Guadalajara Guadalajara Serv.Perif.Consej.Sanidad Toledo Toledo Gestion Hosp. 2000 (Sj Dios) Burgos Burgos Castile and Leon Health Management Areas of León Lion Area Health Management Segovia Segovia Direc. Territ. Saint. And B.Soc Segovia Segovia Health Management Areas of Valladolid Valladolid Hebron Valley General Hospital Barcelona Catalonia Hospital Santa Cruz and San Pablo Barcelona Hebron Valley Children's Hospital Barcelona C. Sanitari del Maresme Mataró University Hospital Arnau Vilanova Lérida San Juan Reus Municipal Hospital Reus Ses-G. Area Badajoz (At.Primaria) Badajoz Estremadura Health Area Management Llerena-Zafra Zafra Don Benito Health Area Management Don Benito


Original Spanish text:
Domicilio social del responsable del producto:
Contribute a better translation

 

[master.on]

Later, many additional batches of Cynomel were recalled
https://www.aemps.gob.es/informa/al...4/docs/calidad_07-2014-cynomel-ampliacion.pdf

As you can see ALL batches from 2394-2404 were recalled.
Too much to be coincidental. Maybe they were indeed cheating by overdosing .

 

[trenboloni]

As your starting post is about 2 years old I assume you figured out a good recipe for t-3? If yes, can you please post it? Thanks.

 

[trenboloni]

And by "good" recipe I mean one that degrades minimally. I am now thinking of using either
1. 1% BA + 99% water
or
2. 100% DMSO

Just need to know which one is better (or if there is a third way)...