Carbetocin API CAS 1631754-28-3

Carbetocin API CAS 1631754-28-3 | Carbetocin acetate cGMP production | Long-acting IUD API | Science-Peptide

Carbetocin API CAS 1631754-28-3 - single dose long lasting prevention of postpartum hemorrhage peptide API.Science-Peptide provides cGMP compliant Carbetocin Acetate with mature process, clear impurity profile, support for China, USA and Europe declarations, and can authorize DMF.Welcome to contact us.

Carbetocin is an "upgraded" form of contractions. Whereas regular contractions can take several hours to administer in an obstetrics department, one intramuscular injection of Carbetocin can keep contractions going for 24 hours or so. For the prevention of postpartum hemorrhage, this is very convenient - especially in under-resourced areas - and can be done in a single injection, without the need for a hangman's bottle.

Its structure is very similar to that of contraction, which is also a 9-peptide ring, but with two modifications: the cysteine at position 1 is deaminated, and the leucine at position 8 is replaced by homocysteine (which is butyrylated). These small changes have extended its half-life from a few minutes to more than 40 minutes, allowing it to act for a longer period of time.

Science-Peptide has been making peptide APIs for more than 20 years, and we have been making cabergoline for a long time. The process is the same as that of IUD, but the cyclization step is more delicate. Currently, we have stable supply of Kapecin acetate API from gram to kilogram, FDA DMF has been filed, and we support China, USA and Europe to declare. In the impurity spectrum, there are mature control schemes for disulfide bond mismatch, oxidized impurities and missing peptides.

Carbetocin is a 9-peptide cyclic form, which is cyclized by a disulfide bond between cysteines at the 1 and 6 positions. The main difference from IUD is that the N-terminus is deamidated (improves enzyme stability) and the 8-position is changed to homocysteine and butyrylated (enhances receptor affinity).

Clinical applications are very focused on:

• Prophylaxis of postpartum hemorrhage (PPH): intramuscular or intravenous infusion in the third stage of labor, given as a single dose. Clinical data show that it is no less effective than continuous infusion of oxytocin in preventing hemorrhage and is more convenient to use.
• Elective cesarean section:Recommended for women with high risk factors for postpartum hemorrhage.
• Not used to induce labor: because of its long duration of action, it is not suitable for initiating labor (once the effect is too strong, it cannot be reversed).

From the API point of view, the market for cabazitaxel is growing fast - as it has been included in the WHO Essential Medicines List, and many countries are upgrading their purchases from contractions to cabazitaxel. The requirements for APIs are also more detailed: the impurity profile should be clean, especially the control of disulfide bond mismatch and 8-position homocysteine-related by-products.

1. The technology is the same as that of the indomethacin, but the cyclization is more precise
The synthesis route of carbenoxolone is similar to that of contraction: synthesis of a linear precursor in the solid phase and cyclization to form a disulfide bond in the liquid phase. However, the spatial configuration of the cyclization is slightly different because the 8-position is homocysteine (one more CH2 than normal cysteine).

• Linear precursor: Fmoc solid-phase synthesis, N-terminal deamidation requires specialized raw materials (deaminated cysteine derivatives), which we have used for many years with stable coupling conditions.
• Cyclization: Mild oxidation in liquid phase. The cyclization efficiency of the disulfide bond of cabergoline is more than 95%, but the mismatch isomers (e.g., 1-1, 6-6 intermolecular disulfide bond) need to be strictly controlled by pH and concentration.
• Purification: Multi-step HPLC preparation: We optimized the purification gradient specifically for cabergoline to separate mismatch isomers, missing peptides, and oxidized impurities.
• Process validation data: The purity was stabilized at over 99.0% and the mismatch isomer was <0.10% in several successive batches.

2. Quality control, with emphasis on mismatched isomers

Each batch is released for testing according to cGMP, covering USP/EP standards, while we pay additional attention to a few key impurities:

• Purity: HPLC ≥99.0%, actual batch 99.2%-99.5%.
• Disulfide bond mismatch isomer: the most critical impurity of cabergoline. We separated it by exclusive HPLC method and controlled it at <0.10%.
• Oxidizing impurities: tyrosine, tryptophan in the sequence? Carbetocin does not have tryptophan, but tyrosine may be oxidized, we control <0.10%.
• Missing peptides: common missing sites with controls, total missing peptides <0.5%.
• Incomplete homocysteine butyrylation: If the side chain butyrylation of the 8-position homocysteine is incomplete, a debutyryl impurity is generated, which we control at <0.15%.
• Endotoxin:<0.25 EU/mg, microbial limit according to Pharmacopoeia.

Stability is done both long term and accelerated, supporting a 24-36 month retest period. Methods are validated.

3. Fully documented and DMF filed

• Reporting information can be used directly: process development reports, process validation programs and reports, analytical method validation, stability data, impurity profiling (mismatched isomers, debutanoyl impurities, etc.), structural confirmation (NMR, MS, IR), batch production records. Cooperate with on-site audits.

DMF has been filed with the US FDA and can be authorized for use in China, the US and Europe.

4. Stable supply chains
Carbetocin uses several specialized amino acids: deaminocysteine and homocysteine derivatives. There are few suppliers of these materials, so we have made safety stock in advance and purchased them from two sources, so that there will be no shortage of supply.
 

• Manufacturing facility 10 acres,cGMP standards,FDA/EMA/NMPA compliance,ISO 9001:2015.
• Synthesis plant: automated solid-phase synthesis, 100 kg capacity
• Purification workshop: multiple sets of preparative HPLC
• Freeze-drying workshop: 30 square meters +, industrial freeze-drying machine
• Clean area: ISO class 7/8
• QC Lab: HPLC, UPLC, LC-MS, GC, etc
• Quality System: Change Control, Deviation Management, CAPA, Supplier Audit, Annual Quality Review. Cooperated with FDA, EMA, NMPA on-site audits.

Domestic pharmaceutical enterprises, Cabergoline injection consistency evaluation: previously looking for suppliers of mismatch isomer fluctuations (0.05%-0.25%). We provided three batches of validation batch, and the mismatch isomer was stabilized at about 0.06%, and we also provided the control product and structure confirmation. They passed the evaluation successfully, and are now purchasing steadily every month.

South American pharmaceutical company: local registration needs to meet the USP standard of cabergoline. We supplied three batches in a row, the purity was above 99.3% and the impurity profile was consistent. They got the registration approval.

Carbetocin is a long-acting choice for obstetrics, with a one-day tube that is convenient and effective. We have accumulated many years of experience in this kind of product, with stable process, fine control of impurities and complete documents. If you are developing the preparation of Cabergoline and need API, please feel free to talk to us.