[QC1] SPECIAL METHODS OF DRUG ANALYSIS

Drug analysis

uses chemical methods or special methods to determine the purity of a material.

Common methods of drug analysis

Ash content determination; Water/ moisture determination; Extractives; Crude fiber determination

Ash content determination

residue left after incineration to dull red heat; represents the inorganic salt content of a crude drug sample; can also a measure of drug adulteration

Dull red heat temperature

550-700 ºC

Acid-insoluble ash

silica content of a crude drug sample obtained after treatment with dilute HCl

Very dull red heat

500 - 550 ºC

Dull red heat

550 - 700 ºC

Bright red heat

800 - 1000 ºC

Yellow red heat

1000 - 1200 ºC

White heat

1200 - 1500 ºC

Ignition to constant weight

continued at 800 ± 25 ºC until 2 consecutive weighing do not differ by > 0.50 mg/g of a substance taken

Drying to constant weight

Drying is continued until 2 consecutive weighing do not differ by > 0.50 mg/g of substance taken

Constant weighing

A point where change in weight after heating and cooling is not more than 0.2 mg

Negligible

quantity not exceeding at 0.5 mg

Loss on ignition

Percentage of test material that is removed given a specified analytical condition

Sulfated ash

Residue in ignition

Loss on drying

Amount if volatile matter that is removed given a specified analytical condition

Ignition

act of strong heating of inorganic matter

Incineration

act of strong heating of organic matter in which ash is the primary residue

Direct ignition

• Magnesium Oxide

• Aluminum monostearate

• Bismuth hydroxide/Bismuth subcarbonate

Precipitation then drying

Sodium chloride, Sodium sulfate, Barium sulfate

Precipitation then Ignition

Magnesium oxide content of magnesium citrate oral solution, Sulfur ointment, Aurothioglucose

Solvent extraction then drying

Amobarbital Na

Method I (water determination)

Karl Fischer: Direct titration, Residual titration, Coulometric Titration (electrolysis)

Ia

Direct titration

Ib

Residual titration

Ic

Coulometric titration

Method II (water determination)

Azeotropic/Toluene distillation Method

Method III (water determination)

Gravimetric method

100 ºC

temperature where H2O will boil or volatilize

Ether-soluble extractives (ESE)

materials that dissolves and volatilizes with ether

Azeotropic method

known as toluene method, xylene method, distillation method

112 ºC

toluene volatilizes, immiscible with H2O and less dense

Titrimetric method

official USP method; known as karl-fischer method

KF reagent

sulfate, iodine, and pyridine (SIMP si Karl)

Sodium Tartrate (Na2C4H4O6 · 2H2O)

primary standard of KF

Canary yellow

endpoint of KF

Water equivalence point

Magnesium of H2O equivalent to 1.0 mL OF KF reagent; standardization of KF reagent

Dew point method

Used to analyze water at very low concentration of the environment; usd only if there is small amount of water

Electrolytic hygrometric method

Uses electric current to determine extremely low water concentration; used if there is only small amount of water

Extractives

constituents of drug samples that are soluble in specific solvents

Maceration

used for non-volatile extraction

Soxhlet

used for continuous extraction

Ether

volatile liquid at room temperature; employs Soxhlet apparatus

Alcohol

determines the amount of resins present in the crude drug sample; uses Soxhlet apparatus

Dilute alcohol

Generic solvent for extracting plant constituents

Hexane

used to determine the amount of fats

Water

used to remove aloe in crude drug samples

Method I (alcohol soluble extract)

Hot Extraction Method

Method II (alcohol soluble extract)

Cold Extraction Method

Crude fiber

residue collected after successive treatment with boiling acid and base; represents cellulose

Physical and chemical constants

measurements of several properties of fats, fatty acids, waxes, balsams, and resins: acid value, unsaponifiable matter, iodine value, hydroxyl value, acetyl value

Acid value

number of milligrams of KOH necessary to neutralize the free acids in 1 g of oil, fat, wax, resin, balsam or similar organic substances of complex composition; also the number of milliliters of 0.1N NaOH required to neutralize free acid in 10 g of substance

Cause of the presence of free acids

hydrolysis of ester; chemical treatment, bacterial action, catalytic action of light and heat

Saponification value

Koettsdorfer number; the number of milligrams of KOH required to neutralize the free acids and saponify the esters contained in 1 g of fat or oil sample

Residual titration with a blank test

instrument used in performing saponification value

Ester value

number of milligrams of KOH required to saponify the esters contains in 1 g of fat or oil sample.

Unsaponifiable matter

substances present in oils or fats that are not saponified by alkali hydroxides, but are soluble in ordinary fat solvents like ether

Phytosterol

Plant origin

Cholesterol

Animal origin

Iodine value/number

number of grams of iodine absorbed under specified conditions by 100 g of oils, fats, and waxes; measure of the degree of unsaturation

Drying oil

IV > 120

Semi- drying oil

100 - 120

Non-drying oil

IV <120

Drying oil example

Linseed oil, Fish oil

Semi-drying oil example

Cottonseed oil, sesame oil

Non-drying oil example

Olive oil, almond oil

Method I (iodine)

Hanus method

Method II (iodine)

Wijs method

Method III (iodine)

Hubi method

Hydroxyl value

number of milligrams of KOH equivalent to the hydroxyl content of 1 g of the substance; Performed via residual filtration with the blank test

Acetyl value

number of milligrams of KOH required to neutralize the acetic acid obtained by the saponification of 1 g acetylated fatty acids

Specific Gravity

determined using a Westphal balance or a pycnometer (official method)

Rotatory Power

determined Laurent half-shadow polarimeter

Refractive index

determined using an Abbe Refractometer

Ester content

performed using residual titration method

Aldehyde/Ketone content determination

Bisulfate method/Hydroxylamine method

Bisulfate Method

water-based method which uses a cassia flask and involves the formation of addition product with Na2S2O3 (H2O-soluble)

Hydroxylamine method

titrimetric method employed when the sample contains other components aside from the aldehyde/ketone or when there is only small amounts of aldehyde/ketone

Salting out principle

a purification technique where precipitation of target molecule is induced in solutions of high ionic strength

Babcock bottle

instrument used for the assay of volatile oil

Proximate analysis

analysis were a class of compounds is determined, e.g. alkaloids

Ultimate analysis

analysis were a specific component within the class is determined, e.g. atropine (from class of alkaloids)

Total moisture

weight before - weight after

Mayer

Potassium mercuric iodide

Dragendorff

Potassium bismuth iodide

Wagneer

Iodine in KI

Marme

Cadmium in potassium iodide

Valser

Mercuric iodide

Scheibler

Phosphotungstic acid

Sonnnchein

Phosphomolybdic acid

Hager

Picric acid

Bouchdart

Iodine in KI