| 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 that has become an essential tool in hepatology, used globally for gallstone dissolution and as first-line therapy for primary biliary cholangitis (PBC). This guide provides pharmaceutical professionals, procurement specialists, and formulators with a thorough reference covering the chemical identity of UDCA, its pharmacological mechanisms, clinical indications, pharmacopoeia requirements, and the practical considerations involved in sourcing UDCA active pharmaceutical ingredient (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 is critical — UDCA is significantly 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 fully 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 is fundamental to its therapeutic application.
UDCA exerts therapeutic effects through four complementary mechanisms. These effects occur concurrently and contribute collectively to the clinical benefit seen 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 is critical. 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 detailed information, see the UDCA product page and our article on UDCA for gallstone dissolution.
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 in liver disease.
UDCA is widely used as 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 a well-established safety profile 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.
| 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 there are notable differences 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 most important 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 specifically limits CDCA to NMT 0.10%, reflecting the high purity expected for pharmaceutical-grade UDCA in the European market. Lithocholic acid, a monohydroxy bile acid with known hepatotoxicity, is separately controlled at NMT 0.15% in the EP.
For a detailed technical comparison, see UDCA Quality Standards: USP vs EP Pharmacopoeia.
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 significantly simplifies the marketing authorization process. Our glossary defines these terms: GMP, CEP, FDA, and pharmacopoeia.
China accounts for the dominant share of global UDCA API production, with estimates suggesting over 70% of the world's pharmaceutical-grade UDCA originates from Chinese manufacturing facilities. The shift from bear bile extraction to fully synthetic production routes was accomplished by Chinese manufacturers in the late 1990s and early 2000s, leveraging 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: Shandong (our home province, home to multiple steroid API manufacturers with established cholic acid supply chains), Jiangsu, Zhejiang, and Tianjin. Each region has its own strengths — Shandong manufacturers typically benefit from proximity to raw material sources, while Jiangsu and Zhejiang facilities often have longer histories of exporting to regulated markets with mature regulatory filing capabilities.
Chinese UDCA suppliers can be broadly classified 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 complete, step-by-step sourcing framework, refer to How to Source UDCA from China: Supplier Selection & Compliance Guide.
UDCA API pricing is influenced by multiple factors. The most significant 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).
Broadly, 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 differential between Tier 1 and Tier 2 material can be significant, reflecting the cost of regulatory maintenance and the premium buyers assign to supply security.
Global UDCA demand has grown steadily 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 raw material position — access to bovine bile as the starting material for cholic acid synthesis — provides a structural cost advantage that is unlikely to be displaced by competitors outside China in the medium term. Environmental regulations in China have led to consolidation among smaller manufacturers over the past decade, reducing the number of active UDCA API producers and contributing to price stability.
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 Shandong 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 are accompanied by comprehensive 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's willingness to provide these documents transparently is itself an important indicator of reliability.