Ropivacaine Hydrochloride

Product Overview

Ropivacaine Hydrochloride (development code LEA-103, brand names Naropin / Narop, Anapeine) was developed by AstraZeneca and is the first long-acting amide local anesthetic marketed as the pure S-(−)-single enantiomer, with enantiomeric purity >99%. Structurally it is built on a piperidine ring core bearing a propyl group on the piperidine nitrogen and a 2,6-dimethylanilide carbonyl at the 2-position; it belongs to the lidocaine-related structural class but contains a tertiary amine side chain.

Mechanism of action: It reversibly blocks voltage-gated sodium channels, inhibiting sodium ion influx and thereby blocking the generation and conduction of nerve fiber impulses. Local anesthetics act similarly on excitable membranes such as brain cells and myocardial cells — when an excessive dose rapidly enters the systemic circulation, central nervous system and cardiovascular toxicity can occur.

“Sensory–motor separation” is its core clinical advantage: high doses produce surgical anesthesia; low doses (2 mg/mL) produce adequate sensory block (analgesia) with only slight, non-progressive motor block, making it especially suitable for postoperative analgesia and labor analgesia — patients retain some motor function while analgesic, and opioid requirements are significantly reduced.

Safety advantages: Compared with bupivacaine, ropivacaine is less lipid-soluble, with lower central nervous system toxicity and cardiac toxicity; its depressant effect on myocardial contractility is weaker than that of (±)-ropivacaine and of (−)- and (±)-bupivacaine. Addition of epinephrine does not alter the intensity or duration of the block. It is metabolized mainly by hepatic CYP1A2 (the main metabolite is 3-hydroxy-ropivacaine).

Technical Specifications

• Standards: CHP / USP / EP
• Specification: 0.99 (purity ≥99.0%, HPLC); ChP, calculated on the anhydrous and solvent-free basis, requires a C₁₇H₂₆N₂O·HCl content of not less than 98.5%
• CAS No.: 132112-35-7 (ropivacaine hydrochloride monohydrate; EINECS 663-286-1; UNII V910P86109; KEGG D04048); anhydrous form 98717-15-8 (UNII 35504LBE2T)
• Molecular formula:
  • Monohydrate: C₁₇H₂₆N₂O·HCl·H₂O (PubChem records the additive formula C₁₇H₂₉ClN₂O₂)
  • Anhydrous: C₁₇H₂₆N₂O·HCl
• Molecular weight:
  • Monohydrate: 328.88 (ChP 328.88; Australian SmPC 328.89; USP reference standard 328.88; PubChem 328.9)
  • Anhydrous: 310.88 (ChP; some databases record 310.86)
  • Exact mass (anhydrous moiety) 310.1812; monoisotopic mass (whole monohydrate) 328.1918
• Appearance: White or almost white crystals or crystalline powder; odorless (ChP); most suppliers describe a white to off-white powder
• Purity (HPLC): ≥ 99.0%
• Melting point: 267–269 °C (consistent across supplier COAs and literature); another source records 269.5–270.6 °C (material recrystallized from acetone–water)
• Specific rotation: −6.5° to −9.0° (ChP official value: prepare a solution in water containing approximately 20 mg per 1 mL and determine according to the method); literature value [α]D²⁰ −7.28° (c=2, water); Sigma reference standard specification [α]/D −9° to −12° (c=1, methanol)
• Chemical name: (S)-(−)-1-propyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide hydrochloride monohydrate (or anhydrous)
• Stereochemistry: Single S-(−)-enantiomer, 1 defined stereocenter, enantiomeric purity >99%
• Solubility: Freely soluble in ethanol, soluble in water, practically insoluble in diethyl ether (ChP); water solubility approx. 50 mg/mL (Australian SmPC), another source records 5 mg/mL (clear); soluble in DMSO, DMF and methanol
• pKa: 8.1 (25 °C); other sources record approx. 8.2
• Solution pH: Saturated solution approx. 4.5; 1% (w/v) aqueous solution approx. 5.0; sparingly soluble above pH 6.0 — precipitation occurs in alkaline environments
• Computed physicochemical parameters: LogP approx. 3.11; topological polar surface area 33.3 Ų (anhydrous moiety 41.57); H-bond donors / acceptors 3 each; rotatable bonds 4
• Storage: Protected from light, tightly closed, refrigerated at 2–8 °C (some reference standards require storage in a desiccator); dosage forms stored at room temperature below 30 °C — avoid freezing

Applications

• Surgical anesthesia: Epidural block (including cesarean section), subarachnoid block, major nerve block (e.g., brachial plexus block), regional block (peripheral nerve block and infiltration anesthesia). Common concentrations 5, 7.5 and 10 mg/mL; lumbar epidural surgical dose 113–200 mg, cesarean section 100–150 mg; onset 10–20 minutes, duration 3–6 hours
• Acute pain management (postoperative analgesia): Continuous epidural infusion or intermittent bolus dosing. The classic regimen establishes the block intraoperatively with 5–7.5 mg/mL and maintains postoperatively with continuous infusion of 2 mg/mL; infusion rates of 6–14 mL/h (12–28 mg/h) provide effective analgesia for most moderate-to-severe postoperative pain with only slight, non-progressive motor block and significantly reduced opioid requirements; clinical experience supports epidural infusion for up to 24 hours (some labeling supports 72 hours)
• Labor analgesia: Lumbar epidural 2 mg/mL, initial dose 20–40 mg, intermittent top-ups of 20–30 mg (minimum interval 30 minutes), or continuous infusion at 6–14 mL/h (12–28 mg/h)
• Pediatric analgesia: The labeling in some countries covers caudal epidural block in children aged 0–12 years, peripheral nerve block in children aged 1–12 years, and continuous epidural infusion (for perioperative and postoperative analgesia)
• Safety and tolerability profile: The most common adverse reactions are hypotension, nausea, vomiting, bradycardia, pyrexia, paresthesia, headache, pruritus and back pain; central nervous system toxicity symptoms generally precede cardiovascular toxicity. A single dose of up to 250 mg in epidural block has been used and well tolerated; cumulative 24-hour doses of 770–800 mg for postoperative analgesia in adults are tolerated
• Formulation and manufacturing: For formulation development of injections (2, 5, 7.5, 10 mg/mL; single-dose vials / infusion bottles), powder for injection (lyophilized) and other dosage forms; key controls include pH (avoid >6.0 to prevent precipitation), related substances, enantiomeric purity (S-enantiomer) and sterility assurance; suitable for analytical method development and validation, stability studies, and GMP scale-up with CMO / CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended solely for compliant industrial, research and pharmaceutical manufacturing use; it is not for end clinical use or guidance for self-administration. The finished product is a prescription drug and must be used by, or under the supervision of, clinicians experienced in regional anesthesia; it is contraindicated in patients hypersensitive to amide local anesthetics. The product’s GHS classification is Serious Eye Damage Category 1 (H318); some suppliers additionally note very toxic by oral, inhalation and dermal routes (R26/27/28). Wear protective gloves, goggles and protective clothing during handling; avoid dust inhalation. Continuous intra-articular infusion is not approved — chondrolysis has been reported. Concomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine, enoxacin) can markedly increase plasma concentrations and should be avoided long-term; concomitant use with Class III antiarrhythmics (e.g., amiodarone) may increase cardiac toxicity — ECG monitoring is recommended.

Product information: please contact us. This information is for reference only.