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C₁₀H₁₆O                                  152.24                                           464-49-3

(1R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one.

Category  Counter-irritant; pharmaceutic aid; antipruritic.

        Natural Camphor is a ketone obtained from Cinnamomum camphora (L.) J. Presl (Family Lauraceae) and purified by sublimation.

Description  Colourless, transparent crystals, crystalline masses, blocks of tough consistence or crumbly masses known as flowers of camphor; odour, strong and characteristic.

Solubility  Slightly soluble in water, very soluble in ethanol and light petroleum, freely soluble in fixed oils, very slightly soluble in glycerol.

Other relevant information 
  1.  Local application to the nostrils of infants may cause immediate collapse.
 2. Liniment containing camphor should not be applied to broken or inflamed skin, mucous membranes, or near the eyes. It readily volatilizes at ordinary temperature.

Packaging and storage  Natural Camphor shall be kept in tightly closed containers, and stored at a temperature not exceeding 25°.

Labelling  The label on the container indicates whether it is obtained from natural sources or is prepared synthetically.

Identification 
  A.  The infrared absorption spectrum is concordant with the spectrum obtained from Racemic Camphor RS or with the reference spectrum of Racemic Camphor.
 B. It complies with the test for Optical rotation.
 C. Dissolve 1 g in 30 mL of methanol, add 1 g of hydroxylamine hydrochloride and 1 g of anhydrous sodium acetate, boil under a reflux condenser for 2 hours, and allow to cool.  Add 100 mL of water, filter, wash the precipitate with 10 mL of water, and recrystallize from 10 mL of a mixture of 4 volumes of ethanol and 6 volumes of water:  the crystals, after drying over phosphorus pentoxide desiccant at a pressure of 1.5 to 2.2 kPa (about 11 to 19 Torr), melt between 118° and 121° (Appendix 4.3).

Melting range  174° to 181° (Appendix 4.3), but using a capillary tube with an internal diameter of not greater than 2 mm.

Optical rotation  +40° to +43° at 20°, determined in a 10.0 per cent w/v solution in ethanol (Appendix 4.8).

Water  Dissolve 1 g  in 10 mL of petroleum ether (boiling range, 40° to 60°):  the solution is clear (Appendix 4.1).

Halogens  Not more than 100 ppm.  To 10.0 mL of a 10.0 per cent w/v solution in 2-propanol in a distillation flask, add 1.5 mL of 2 M sodium hydroxide and 50 mg of Raney nickel catalyst, heat on a water-bath until the solvent has evaporated and allow to cool.  Add 5 mL of water, mix, filter through a wet filter paper previously washed with water until free from chloride, and dilute the filtrate to 10.0 mL with water.  To 5.0 mL of this solution add nitric acid dropwise until the precipitate that is produced dissolves and add sufficient water to produce 20 mL.  The resulting solution shows no more chloride than that corresponds to 0.07 mL of 0.020 M hydrochloric acid.

Related substances  Carry out the test as described in the “Gas Chromatography” (Appendix 3.4).  
 Standard solution (a)  Dilute 1.0 mL of Test solution to 100.0 mL with heptane.
  Standard solution (b)  Dilute 10.0 mL of Standard solution (a) to 20.0 mL with heptane.
 Standard solution (c)  Dissolve 500 mg of borneol in heptane and dilute to 25.0 mL with the same solvent.  Dilute 5.0 mL of the solution to 50.0 mL with heptane.
 Standard solution (d)  Dissolve 50 mg of linalool and 50 mg of bornyl acetate in heptane and dilute to 100.0 mL with the same solvent.  
 Test solution  Dissolve 2.5 g of the sample in heptane and dilute to 25.0 mL with the same solvent. Chromatographic system.
   Detector  Flame ionization
   Column  A glass column (30 m × 0.25 mm) packed with macrogol 20000 (0.25 µm).
  Temperature 
    Column  The temperature programme is as follows:

                      Injection port 220° 
                      Detector 250°
                Carrier gas  Helium 
                Split ratio  1:70
               Flow rate  45 cm per second (1.3 mL per minute)
        System suitability
               Sample  Standard solution (d) 
         Suitability requirements
                Resolution  Not less than 3.0 between bornyl acetate and linalool peaks.
        Procedure  Inject a portion (about 1 mL) of Standard solution (a), Standard solution (b), Standard solution (c), Standard solution (d), and Test solution into the chromatograph.  Measure the area of the principal peak in each chromatogram.
 Limits 
 — borneol:  not more than the area of the principal peak in the chromatogram obtained from standard solution (c) (2.0 per cent).
 — any impurity:  not more than half of the area of the principal peak in the chromatogram obtained from standard solution (a) (0.5 per cent).
 — total of other impurities:  not more than 4 times the area of the principal peak in the chromatogram obtained from standard solution (a) (4.0 per cent).
 — disregard limit:  0.1 times the area of the principal peak in the chromatogram obtained from standard solution (b) (0.05 per cent).

Non-volatile matter  Not more than 0.1 per cent w/w when volatilized at 105° to constant weight; use about 
 5 g, accurately weighed.

Assay  Carry out the determination as described in the “Gas Chromatography” (Appendix 3.4).   
 Internal standard preparation  Dissolve about 2 g of methyl salicylate, accurately weighed, in 50.0 mL of absolute ethanol.
 Standard preparation  Weigh accurately about 100 mg of Natural Camphor RS, add 5.0 mL of Internal standard preparation, dissolve in absolute ethanol and dilute to 100.0 mL with the same solvent. 
 Assay preparation  Weigh accurately about 100 mg of Natural Camphor, add 5.0 mL of Internal standard solution, dissolve in absolute ethanol and dilute to 
 100.0 mL with the same solvent.
 Chromatographic system
   Detector  Flame ionization
   Column  A glass column (3 m × 3 mm) packed with 10 per cent of polyethylene glycol 20 M on silanized diatomaceous support 180- to 250-mesh.
  Temperature 
    Column 160° 
  Carrier gas  Nitrogen 
   Flow rate  Adjust so that the retention time of natural camphor is about 6 minutes.
 System suitability 
   Sample  Standard  preparation  

 Suitability requirements
   Resolution  Not less than 7 between natural camphor and methyl salicylate peaks.
   Relative standard deviations Chromatog-raph six injections of Standard preparation, and record peak areas. The analytical system is suitable for conducting this Assay if the relative standard deviation for the area ratios of natural camphor to methyl salicylate is not more than 1.0 per cent.  
 Procedure  Separately inject equal volumes (about 2 µL) of Standard preparation and Assay preparation into the chromatograph, record the chromatograms and measure the areas of natural camphor and methyl salicylate peaks.  Calculate the area ratios of natural camphor to methyl salicylate peaks. 
  Calculation  Calculate the content of C₁₀H₁₆O in the portion of Natural Camphor taken, using the declared content of C₁₀H₁₆O in Natural Camphor RS.