Rocuronium Bromide

Product Overview

Rocuronium Bromide (ORG 9426) is an aminosteroid non-depolarizing neuromuscular blocking agent, structurally a derivative of vecuronium: a 5α-androstane skeleton with a morpholine ring at the 2β position, a hydroxyl group at 3α, an N-allylpyrrolidinium at 16β (a quaternary ammonium cation, forming a salt with bromide) and an acetate at 17β.

Clinical positioning as “fastest onset”: Rocuronium is the fastest-onset non-depolarizing muscle relaxant in common clinical use. At clinically usual doses, onset time is 50–90 seconds — about 90 seconds after intravenous injection of 0.6 mg/kg, good tracheal intubation conditions are achieved; when the dose is increased to 0.9–1.0 mg/kg, intubation is possible in about 60 seconds. This makes it an important alternative to succinylcholine in rapid sequence induction (RSI).

Potency and time course: Its potency is about 1/6–1/8 that of vecuronium, and its duration about 2/3 that of vecuronium. ED95 approx. 0.3 mg/kg; intubation dose 0.6–1.0 mg/kg; clinical duration 45–60 minutes; maintenance dose 0.1–0.15 mg/kg. It belongs to the intermediate-acting category.

Mechanism of action: After binding to cholinergic receptors at the motor endplate, it does not alter the membrane potential of the motor endplate but prevents acetylcholine from binding to the receptor, thereby producing muscle relaxation — unlike depolarizing muscle relaxants, muscle relaxation is not preceded by muscle fiber fasciculation. The literature also records that it inhibits postsynaptic nicotinic acetylcholine receptors (nAChR) and has some inhibitory effect on M2/M3 muscarinic receptors (an effect associated with its occasional tachycardia).

Pharmacokinetic profile: Mainly taken up by the liver and excreted in bile, partly excreted renally; the duration of action may be prolonged in patients with hepatic impairment, renal impairment and in the elderly.

Technical Specifications

• Standards: CHP / USP / EP

• Specification: 0.99 (purity ≥99.0%, HPLC); the ChP monograph requires, calculated on the anhydrous and solvent-free basis, a C₃₂H₅₃BrN₂O₄ content of 98.0%–102.0%; the dosage-form monograph (injection) requires rocuronium bromide content of 93.0%–107.0% of the labeled amount

• CAS No.: 119302-91-9 (EINECS 601-597-6; MDL MFCD00867768; PubChem CID 441351)

• Molecular formula: C₃₂H₅₃BrN₂O₄

• Molecular weight: 609.68 (Sigma-Aldrich EP reference standard, LKT, TCI, ChemicalBook); ChP and Chinese labeling record 609.70 (rounding difference); some sources record 609.678 / 609.69

• Appearance: Off-white to slightly yellow powder; hygroscopic (ChP monograph). Other descriptions include “almost white or pale yellow, slightly hygroscopic powder” (BP / EP) and “white to off-white crystalline powder” (suppliers)

• Purity (HPLC): ≥ 99.0%

• Melting point: 162–164 °C (consistent across Thermo Fisher, LKT, TCI, Viva Supply, Jizhi Biochemical and other sources — recommended). Literature also records 161–164 °C (decomposition) and a broader range of 161–169 °C. Note: the ChP monograph’s [Description] section does not include a melting point; the above values come from reagent / supplier standards and literature, not official pharmacopoeial values; when adopted they should be labeled as “in-house / literature values”

• Specific rotation: +28.5° to +32.0° (ChP official value: dissolve the substance in 0.1 mol/L hydrochloric acid solution to prepare a solution containing approximately 10 mg per 1 mL and determine according to the method). A literature value of [α]D²⁰ +18.7° (c=1.03, chloroform) also exists — solvent and concentration differ; the values are not mutually comparable

• Chemical name: 1-allyl-1-[3α,17β-(dihydroxy)-2β-(morpholin-1-yl)-5α-androstan-16β-yl]pyrrolidinium bromide 17-acetate; IUPAC: 1-[(2β,3α,5α,16β,17β)-17-(acetyloxy)-3-hydroxy-2-(4-morpholinyl)androstan-16-yl]-1-(2-propenyl)pyrrolidinium bromide

• Stereochemistry: The steroidal core contains multiple defined stereocenters (2β, 3α, 5α, 16β, 17β)

• Solubility (ChP): Very soluble in ethanol, freely soluble in water or dichloromethane, practically insoluble in diethyl ether, very soluble in 0.1 mol/L hydrochloric acid solution. Other sources describe: freely soluble in water (100 mg/mL, clear, pale yellow) and anhydrous ethanol, very soluble in dichloromethane, sparingly soluble in chloroform. Reagent grade: water approx. 112 mg/mL; DMSO and ethanol approx. 113 mg/mL

• Computed physicochemical parameters: Density approx. 1.32 g/cm³ (predicted)

• Dosage form parameters: The injection is a colorless to slightly yellow clear liquid; common strengths in China are 2.5 mL:25 mg and 5 mL:50 mg (i.e., 10 mg/mL); excipients include sodium acetate and sodium chloride

• Storage: Sealed, protected from light, store at 2–8 °C (do not freeze); the API should be kept in a tight container, protected from moisture and light; some reference standards recommend frozen storage at −20 °C

Applications

• Tracheal intubation during routine induction of anesthesia (core indication): Intravenous injection of 0.6 mg/kg in adults provides good intubation conditions after 90 seconds, with a duration of 30–45 minutes; for rapid tracheal intubation the dose is increased to 0.9 mg/kg, achieving good intubation conditions in 60 seconds, with muscle relaxation maintained for up to about 75 minutes. Also suitable for rapid sequence induction (RSI)

• Maintenance of intraoperative muscle relaxation: Intermittent intravenous maintenance doses of 0.15 mg/kg; reduced to 0.075–0.1 mg/kg in patients on prolonged inhalational anesthetics. Maintenance doses are best given when twitch height has recovered to 25% of control, or when 2–3 responses to train-of-four (TOF) stimulation appear. Continuous intravenous infusion: an intravenous loading dose of 0.6 mg/kg is recommended first; once muscle relaxation begins to recover, switch to an infusion, adjusting the rate to maintain twitch height at about 10% of control or 1–2 TOF responses; 5–10 μg/(kg·min) during intravenous general anesthesia, 5–6 μg/(kg·min) during inhalational general anesthesia

• Dose adjustment in special populations: Elderly patients and patients with hepatic or renal impairment — intubation dose 0.6 mg/kg, maintenance dose 0.075–0.1 mg/kg intravenously or 5–6 μg/(kg·min) by infusion; obese patients (body weight exceeding standard weight by 30% or more) show prolonged duration and delayed recovery of spontaneous breathing when dosed on actual body weight — body composition should be considered and the dose appropriately reduced; patients with toxemia of pregnancy receiving magnesium salts should receive reduced doses; patients with myasthenia gravis or Eaton–Lambert syndrome may show a strong response to small doses and should be titrated to response; burn patients (area >30%, days 5–70 post-injury) may develop resistance and require adjustment according to response

• Pediatric use: Infants (1 month–12 months) and children (1–14 years) show faster onset and shorter duration than adults; intubation dose 0.6 mg/kg, maintenance dose 0.15 mg/kg

• Pharmacology and mechanism research: For research on competitive antagonism of nicotinic acetylcholine receptors, evaluation of M2/M3 muscarinic receptor inhibition, structure–activity relationships of aminosteroid muscle relaxants, neuromuscular monitoring methodology (TOF, PTC), and antagonism studies with sugammadex (the specific reversal agent) and neostigmine

• Formulation and manufacturing: For formulation development of injections (10 mg/mL; strengths 2.5 mL:25 mg, 5 mL:50 mg); excipients are sodium acetate and sodium chloride. Key production control points include related substances (especially 2β/16β isomers and the deacetylated product), assay (98.0%–102.0% on the anhydrous, solvent-free basis), specific rotation (+28.5° to +32.0°), moisture (the API is hygroscopic) and pH; suitable for analytical method development and validation, stability studies, impurity reference standards, 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 in settings equipped for tracheal intubation, artificial ventilation and oxygen resuscitation, by trained anesthesiologists. Contraindication: hypersensitivity to this product or to bromide ions. Neuromuscular function, heart rate, blood pressure and assisted ventilation status should be monitored during use; if respiratory muscle paralysis occurs, artificial respiratory support should be given until spontaneous breathing recovers. Patients should not drive or operate machinery within 24 hours after use. Use with caution in: neuromuscular diseases (myasthenia gravis, myasthenic syndrome, poliomyelitis), obesity, electrolyte disturbances (hypokalemia, hypermagnesemia, hypocalcemia), hypoproteinemia, dehydration, acid–base imbalance, cachexia, hepatic, renal and biliary disease, cardiovascular disease, burns, sepsis and long-term bedridden patients. Drug interactions: inhalational anesthetics (enflurane, isoflurane, halothane), succinylcholine, aminoglycoside and polypeptide antibiotics, diuretics, quinidine, magnesium salts, calcium channel blockers and lithium salts can potentiate its effect; neostigmine, edrophonium, pyridostigmine, norepinephrine, azathioprine, theophylline, calcium chloride, phenytoin sodium, carbamazepine and long-term corticosteroid use can attenuate its effect. The API’s GHS classification is Acute Oral Toxicity Category 3 (H301) and Specific Target Organ Toxicity (respiratory irritation) Category 3; some sources additionally note H302/H315/H319/H335. Wear protective gloves, protective clothing, and respiratory, eye and face protection during handling; avoid dust inhalation.

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