| CAS Number | 128-13-2 |
|---|---|
| Molecular Formula | C24H40O4 |
| Molecular Weight | 392.57 g/mol |
| Pharmacopoeia | EP / USP |
| Packaging | 25 KG/DRUM |
| Chemical Class | Secondary bile acid |
| Natural Source | Bear bile (historically); now synthetic |
| Discoverer | Hammarsten (1902) |
Ursodeoxycholic acid (UDCA) is a secondary bile acid used worldwide for gallstone dissolution and as first-line therapy for primary biliary cholangitis (PBC). This guide covers UDCA's chemical identity, how it works, its clinical uses, pharmacopoeia standards, and what to look for when sourcing UDCA API from China.
Ursodeoxycholic acid (CAS 128-13-2) is a naturally occurring hydrophilic bile acid. It has the molecular formula C24H40O4 and a molecular weight of 392.57 g/mol. Its IUPAC name is 3α,7β-dihydroxy-5β-cholan-24-oic acid. Structurally, UDCA is the 7β-epimer of chenodeoxycholic acid (CDCA); the two differ only in the orientation of the hydroxyl group at the C-7 position of the steroid nucleus. This stereochemical difference matters: UDCA is more hydrophilic and less cytotoxic than its 7α-epimer.
UDCA was first identified by the Swedish biochemist Olof Hammarsten in 1902, who isolated it from the bile of polar bears (Ursus maritimus), hence the name "urso-" from the Latin ursus for bear. UDCA constitutes a minor fraction (approximately 1-3%) of total bile acids in healthy human bile, compared with approximately 40% each of cholic acid and chenodeoxycholic acid. Historically, commercial UDCA was extracted from bear bile, but modern pharmaceutical production uses a synthetic route starting from cholic acid obtained from bovine bile, followed by selective epimerization of the 7α-hydroxyl group. This synthetic approach eliminated dependence on endangered bear species and aligned UDCA production with CITES (Convention on International Trade in Endangered Species) requirements.
In healthy hepatobiliary physiology, UDCA is formed in the distal small intestine and colon by the 7-epimerization of CDCA by intestinal bacteria. UDCA then undergoes enterohepatic circulation, where it competes with more hydrophobic and cytotoxic endogenous bile acids at the canalicular membrane, shifting the bile acid pool toward a less toxic composition. This property underlies its therapeutic use.
UDCA works through four mechanisms that operate together in cholestatic liver disorders.
UDCA stimulates bicarbonate-rich bile secretion (choleresis) at the bile canaliculus. It achieves this by inserting into the canalicular membrane and upregulating the expression and insertion of transport proteins ( including the bile salt export pump (BSEP, ABCB11), the multidrug resistance protein 3 (MDR3, ABCB4), and the anion exchanger 2 (AE2, SLC4A2) ) via post-transcriptional mechanisms. The resulting increase in bile flow helps flush toxic bile acids from the hepatocyte, reducing intrahepatic bile acid retention.
In cholestatic conditions, hydrophobic bile acids such as glycochenodeoxycholic acid and taurochenodeoxycholic acid accumulate and cause hepatocellular damage through detergent-like solubilization of plasma membranes, mitochondrial dysfunction, and induction of apoptosis. UDCA treatment enriches the bile acid pool with up to 40-60% UDCA, displacing toxic hydrophobic species. UDCA and its conjugates also stabilize mitochondrial and plasma membranes against bile-acid-induced injury, reducing the release of alanine aminotransferase (ALT) and other markers of hepatocyte damage.
Hydrophobic bile acids activate the Fas death receptor pathway, leading to caspase activation and hepatocyte apoptosis. UDCA prevents this by inhibiting mitochondrial membrane permeability transition, reducing cytochrome c release, and blocking the translocation of Bax from cytosol to mitochondria. These effects have been observed in cultured hepatocytes at UDCA concentrations achieved clinically with doses of 10-15 mg/kg/day.
UDCA downregulates the aberrant expression of HLA class I molecules on hepatocytes and biliary epithelial cells, a hallmark of PBC. It also reduces the production of IgM and IgG autoantibodies and diminishes the activity of autoreactive T-cell responses against the pyruvate dehydrogenase complex (PDC-E2). These immunomodulatory actions are distinct from the direct hepatoprotective mechanisms and may contribute to the delay in histological progression observed in long-term PBC studies.
UDCA is indicated for the oral dissolution of radiolucent, non-calcified cholesterol gallstones smaller than 20 mm in diameter, in patients with a functioning gallbladder and a patent cystic duct. The standard dose is 8-10 mg/kg/day, administered in divided doses or as a single bedtime dose. Dissolution rates depend on stone characteristics: for small (<5 mm) radiolucent stones, complete dissolution is achieved in approximately 60% of patients over 6 months, rising to 80-90% over 12-24 months in selected populations. For stones 5-20 mm, dissolution rates are lower, with 30-50% achieving complete dissolution over 12-24 months. Calcified or pigmented stones are not suitable for UDCA dissolution therapy.
Patient selection matters. Ultrasound confirmation of gallstone type, size, and number must be obtained before initiating therapy. Non-invasive monitoring at 6-month intervals is recommended. After successful dissolution, approximately 25-50% of patients will develop recurrent stones within 5 years if treatment is discontinued without maintenance dosing. For more information, see the ursodeoxycholic acid (UDCA) API manufacturer page and our article on UDCA gallstone dissolution: dosing, efficacy, and patient selection.
PBC is a chronic, progressive cholestatic liver disease characterized by autoimmune destruction of intrahepatic bile ducts. UDCA at a dose of 13-15 mg/kg/day is the FDA-approved first-line treatment and is recommended by both the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL). In PBC, UDCA improves serum liver biochemistries (alkaline phosphatase, ALT, gamma-GT, bilirubin), reduces the rate of histological progression, and delays the need for liver transplantation. Biochemical response is typically assessed after 6-12 months of therapy using criteria such as the Paris I, Paris II, Barcelona, or Toronto definitions. Patients who achieve an adequate biochemical response (approximately 60-70%) have a transplant-free survival comparable to that of the age- and sex-matched general population.
UDCA use in PSC remains controversial. Standard-dose UDCA (13-15 mg/kg/day) has been shown to improve liver biochemistry in some studies but has not demonstrated a statistically significant survival benefit in randomized controlled trials. High-dose UDCA (28-30 mg/kg/day) was associated with an increased risk of adverse outcomes (death, liver transplantation, varices, or cholangiocarcinoma) in a 2009 randomized trial by Lindor et al., and high-dose therapy is no longer recommended for PSC. For more information, refer to our article on UDCA liver disease treatment: PBC, PSC, and NASH applications.
UDCA is the standard first-line pharmacotherapy for ICP, at doses of 10-20 mg/kg/day. Several randomized controlled trials and a 2019 meta-analysis have shown that UDCA improves maternal pruritus and serum liver enzymes and may reduce the risk of preterm birth. UDCA crosses the placenta at low levels and has an established safety record in pregnancy based on over two decades of clinical use, though it is used off-label for this indication in many jurisdictions.
UDCA has been investigated in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) with mixed results. While it reliably reduces ALT levels, histological improvement has not been consistently demonstrated across studies. UDCA is also used in pediatric cholestatic disorders, cystic fibrosis-associated liver disease, and for gallstone prevention during rapid weight loss (particularly following bariatric surgery), typically at a dose of 600 mg/day divided in two or three doses.
Both the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) publish clinical practice guidelines for the management of cholestatic liver diseases that include specific UDCA recommendations. These udca guidelines are the authoritative reference for clinicians prescribing UDCA worldwide.
PBC Dosing and Monitoring (AASLD/EASL). Both AASLD and EASL recommend UDCA at 13-15 mg/kg/day as first-line treatment for all PBC patients, administered as a single daily dose (typically at bedtime). This dosing is supported by meta-analysis data showing that doses below 13 mg/kg/day are associated with lower transplant-free survival. UDCA should be continued lifelong, including during pregnancy and breastfeeding, where it has an established safety record. Liver biochemistry (ALP, ALT, GGT, bilirubin) should be monitored every 3 months during the first year of therapy.
Biochemical Response Assessment. Per AASLD and EASL udca guidelines, biochemical response to UDCA should be formally assessed after 12 months of therapy using validated criteria such as the Paris I, Paris II, Barcelona, or Toronto definitions. Patients achieving an adequate biochemical response (approximately 60-70% of patients) have a transplant-free survival comparable to the age- and sex-matched general population. For patients with inadequate response, the GLOBE score and UK-PBC Risk Score are recommended tools for risk stratification and treatment escalation decisions. The 2024-2025 guideline updates introduced three new FDA-approved second-line agents (obeticholic acid, elafibranor, and seladelpar) for UDCA-inadequate responders.
Safety Note. High-dose UDCA (over 20 mg/kg/day) is not recommended. A 2009 randomized trial by Lindor et al. found that high-dose UDCA (28-30 mg/kg/day) in PSC was associated with more adverse outcomes including death, liver transplantation, varices, and cholangiocarcinoma. Both AASLD and EASL guidelines now carry this safety caution across cholestatic indications.
| Indication | Typical Dose (mg/kg/day) | Duration | Evidence Level |
|---|---|---|---|
| Gallstone dissolution | 8-10 | 6-24 months | Well-established |
| Primary biliary cholangitis (PBC) | 13-15 | Long-term / indefinite | FDA-approved; first-line |
| Primary sclerosing cholangitis (PSC) | 13-15 (standard); high-dose contraindicated | Variable | Controversial; improvement in labs but not survival |
| Intrahepatic cholestasis of pregnancy (ICP) | 10-20 | Until delivery | Well-established (off-label) |
| Gallstone prevention (bariatric weight loss) | 600 mg/day total | During rapid weight loss phase | Established guideline recommendation |
| NAFLD / NASH | 13-15 | 12-24 months | Experimental; mixed evidence |
UDCA API is supplied against two principal pharmacopoeia monographs: the United States Pharmacopeia (USP) and the European Pharmacopoeia (EP). Both monographs specify identification, assay, purity, and impurity limits, but they differ in acceptance criteria and test methodology.
| Parameter | USP | EP |
|---|---|---|
| Assay (HPLC, anhydrous basis) | 98.0-102.0% | 99.0-101.0% |
| Related substances, individual impurity | ≤ 0.5% | ≤ 0.10% (chenodeoxycholic acid); ≤ 0.15% (lithocholic acid); ≤ 0.10% (any other) |
| Related substances, total impurities | ≤ 2.0% | ≤ 0.5% |
| Specific rotation [α]D20 | +58.0° to +62.0° | +58.0° to +62.0° (anhydrous) |
| Loss on drying | ≤ 1.0% | ≤ 1.0% |
| Heavy metals | ≤ 20 ppm | ≤ 20 ppm (method A) |
| Residual solvents | ICH Q3C | ICH Q3C (Ethanol ≤ 5000 ppm) |
| Microbial limits | As per USP <61>/<62> | TAMC ≤ 1000 CFU/g; TYMC ≤ 100 CFU/g |
The primary quality indicator is the related substances (impurity) profile. Chenodeoxycholic acid (CDCA) is the primary process-related impurity in synthetic UDCA because it is the C-7 epimer from which UDCA is produced. The EP monograph requires control of CDCA, lithocholic acid, and other related bile acids. High-purity EP-grade UDCA typically controls CDCA to NMT 0.10% and lithocholic acid to NMT 0.15%, reflecting the purity expected for pharmaceutical-grade UDCA in the European market. Lithocholic acid, a monohydroxy bile acid with known hepatotoxicity, is separately controlled. [citation needed]
For a detailed technical comparison, see UDCA quality standards: USP vs EP pharmacopoeia comparison.
A Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) is issued by the European Directorate for the Quality of Medicines & HealthCare (EDQM) and certifies that the UDCA manufacturing process complies with the relevant EP monograph. CEP holders are subject to periodic GMP inspections. For API entering the European market, a CEP simplifies the marketing authorization process. Our glossary defines these terms: GMP, CEP, FDA, and pharmacopoeia.
When evaluating a potential UDCA supplier China, verify GMP certification, DMF/CEP filing status, and batch-to-batch consistency data. China accounts for over 70% of global UDCA production, making it the primary source for UDCA API China price comparison and UDCA wholesale China procurement. As an established ursodeoxycholic acid manufacturer China, KingWish exports 40+ MT of UDCA annually to pharmaceutical manufacturers worldwide. For buyers looking to buy UDCA bulk, we offer 25 KG/DRUM standard packaging with trial quantities available. Contact us for ursodeoxycholic acid China export documentation and CoA review.
China accounts for the largest share of global UDCA API production. Over 70% of the world's pharmaceutical-grade UDCA comes from Chinese manufacturing facilities. The shift from bear bile extraction to synthetic production routes was accomplished by Chinese manufacturers in the late 1990s and early 2000s, using the country's established steroid chemistry infrastructure and large-scale cholic acid supply chain derived from bovine bile, a byproduct of the domestic beef industry.
UDCA API manufacturing in China is concentrated in several provinces with established steroid chemistry infrastructure, including Guangdong (where KingWish's partner factory is located, in Zhongshan), Jiangsu, Zhejiang, and Tianjin. Guangdong and Shandong manufacturers are closer to raw material sources, while Jiangsu and Zhejiang facilities tend to have longer histories of exporting to regulated markets with mature regulatory filing capabilities.
Chinese UDCA suppliers fall into three tiers. Tier 1 suppliers hold active DMFs with the US FDA and/or valid CEPs with the EDQM, operate under regular GMP inspections, and supply directly to multinational pharmaceutical companies. Tier 2 suppliers maintain GMP-compliant operations and may hold one or more regulatory filings but typically supply through trading partners rather than directly to innovator companies. Tier 3 suppliers are smaller manufacturers or intermediaries without significant regulatory filings; they may offer competitive pricing but carry greater compliance risk for regulated market buyers. For a directory of ursodeoxycholic acid API manufacturers by region, see our supplier landscape guide.
For a step-by-step framework on vetting suppliers, see how to source UDCA API from China: supplier selection, compliance checks, and audit guide.
UDCA API pricing is driven by several factors. The biggest is the purity grade, EP-grade UDCA with a CEP commands a premium over USP-grade material due to stricter impurity specifications and the cost of maintaining EDQM regulatory filings. Order volume is the second major driver: standard commercial quantities (100-500 kg) benefit from economies of scale compared to evaluation samples (1-5 kg) or small development batches (25-50 kg).
Three price tiers exist in the current market: (1) EP-grade with an active CEP, representing the highest quality and regulatory assurance level; (2) EP/USP-grade manufactured under GMP but without an active CEP or DMF, suitable for certain regulated and non-regulated markets; (3) non-pharmacopoeia grade for non-pharmaceutical applications (e.g., research, dietary supplements in less regulated markets). The price gap between Tier 1 and Tier 2 material reflects the cost of regulatory maintenance and the premium buyers place on supply security.
Global UDCA demand has grown, driven by rising PBC diagnosis rates (approximately 2-4 per 100,000 person-years globally), expanding off-label use in NAFLD/NASH, and the aging population with increased gallstone prevalence. China's access to bovine bile as the starting material for cholic acid synthesis gives it a structural cost advantage that is hard for competitors outside China to match. Environmental regulations in China have consolidated smaller manufacturers over the past decade, reducing the number of active UDCA API producers and stabilizing prices.
KingWish supplies over 40 metric tons of UDCA API annually to pharmaceutical manufacturers, trading companies, and formulators in 100+ countries. Our supply chain is anchored by long-term strategic partnerships with GMP-certified manufacturers in Zhongshan, Guangdong province, providing consistent quality and reliable delivery schedules. We supply EP-grade and USP-grade UDCA in standard 25 KG/drum packaging, with the flexibility to accommodate customer-specific packaging and labeling requirements.
All UDCA shipments come with full documentation: Certificate of Analysis (CoA) issued by the manufacturer's quality control laboratory, Material Safety Data Sheet (MSDS), and relevant regulatory certificates. Third-party laboratory verification is available upon request. Our supply meets EP and USP monographs, and we support customers with DMF and CEP documentation where the manufacturing facility holds such filings.
For detailed product specifications, current pricing, and lead time information, visit the UDCA product page or contact Thomas Qiao directly at THOMASQIAO@KINGWISH.CN or by telephone at 0086 532 85065286.
UDCA (ursodeoxycholic acid) is the unconjugated free acid. TUDCA (tauroursodeoxycholic acid) is the taurine conjugate of UDCA. In the body, UDCA is conjugated with taurine (predominantly) or glycine in the liver before secretion into bile. TUDCA is more water-soluble than UDCA and is sometimes used in research settings and as a dietary supplement. Pharmaceutical products for human therapeutic use are formulated with UDCA, not TUDCA, and UDCA capsules/tablets are the registered drug product form in all major pharmacopoeias.
At minimum, request: (1) a current Certificate of Analysis (CoA) from a recent production batch, (2) a Method of Analysis document detailing the test procedures, (3) evidence of GMP compliance (GMP certificate or inspection report), (4) the manufacturer's DMF status and CEP status if applicable, (5) a Product Quality Standard Sheet or Specification Sheet, and (6) an MSDS. For regulated markets, request documentation on the manufacturer's regulatory filing history with the FDA or EDQM. A supplier who provides these documents without hesitation is usually more reliable.