USP藻酸盐测定ALGINATES ASSAY

USP 35Chemical Tests / ?311? Alginates Assay153

beaker, add water to make a total volume of about 70 mL, 3.5. Calculate the number of mEq of acid consumed by the and mix on the Magnetic Stirrer for 1 minute.Tablet tested by the formula:

Lozenges—Accurately weigh not fewer than 20 lozenges,

Total mEq = (30 × N HCl) – (V NaOH× N NaOH)

and determine the average weight. Select and weigh 2 loz-

enges, and transfer them to a 250-mL beaker containing 70

in which the terms are as defined above.

mL of water.

Nonchewable Tablets—Weigh not fewer than 20 tablets,

and determine the average tablet weight. Grind the tablets

to a fine powder, mix to obtain a uniform mixture, and

transfer an accurately weighed quantity of it, equivalent to

the minimum labeled dosage, to a 250-mL beaker. If wet-

ting is desired, add not more than 5 mL of alcohol (neutral-?311? ALGINATES ASSAY

ized to an apparent pH of 3.5), and mix to wet the speci-

men thoroughly. Add 70 mL of water, and mix on the

Magnetic Stirrer for 1 minute.

Chewable Tablets—Prepare as directed for Nonchewable

Tablets.APPARATUS Tablets That Are Required To Be Chewed—Transfer 1 Tablet

to a 250-mL beaker, add 50 mL of water, and mix on the The required apparatus (see Figure 1) contains a capillary Magnetic Stirrer for 1 minute.metering valve, A, followed by a flowmeter, B, to control Capsules—Weigh accurately not fewer than 20 capsules.and monitor the flow of nitrogen through the system. Halo-Remove the capsule contents completely, with the aid of a genated vinyl plastic tubing* and a rubber fitting, C, are cotton swab if necessary. Accurately weigh the empty cap-used to connect the flowmeter to a sidearm of a reaction sules, and determine the average weight of the contents per flask, D. Flask D is a 250-mL round-bottom, boiling flask, capsule. Mix the combined capsule contents to obtain a resting in a suitable heating mantle, E. Flask D is provided uniform mixture, and proceed as directed for Nonchewable with a 225-mm Hopkins coil reflux condenser, F. The con-Tablets, beginning with “transfer an accurately weighed denser terminates in a U-shaped trap, G, which contains quantity of it.”two 25-g bands of 20-mesh zinc, the bands being bounded Procedure for Powders, Effervescent Solids,and separated by three 3-inch plugs of glass wool. The trap Suspensions and Other Liquids, Lozenges, Nonchewable terminates in an adapter, H, that by means of a haloge-Tablets, Chewable Tablets, and Capsules—Pipet 30.0 mL nated vinyl plastic tubing and a twistcock connector, I, con-of 1.0 N hydrochloric acid VS into the Test Preparation while nects with a 250-mL gas washing bottle, J. The inlet (bub-continuing to stir with the Magnetic Stirrer. [N OTE—Where bling) tube extends almost to the bottom of the gas

the acid-neutralizing capacity of the specimen under test is washing bottle, and it terminates in a fritted disk having a greater than 25 mEq, use 60.0 mL of 1.0 N hydrochloric coarse porosity. The size of all glass joints is 24/40, except for acid VS, and make the appropriate modifications in the cal-the 45/50 joint of the gas washing bottle.

culation.] Stir for 15 minutes, accurately timed, after the

addition of the acid, begin to titrate immediately, and in a

period not to exceed an additional 5 minutes, titrate the

excess hydrochloric acid with 0.5 N sodium hydroxide VS to

attain a stable (for 10 to 15 seconds) pH of 3.5. Calculate

the number of mEq of acid consumed by the formula:

Total mEq = (30 × N HCl) – (V NaOH× N NaOH)

in which N HCl and N NaOH are the normalities of the hydro-

chloric acid VS and the sodium hydroxide VS, respectively;

and V NaOH is the volume of sodium hydroxide VS used for

titration. Express the result in terms of mEq of acid con-

sumed per g of the substance tested.

Procedure for Tablets That Are Required To Be

Chewed—Pipet 30.0 mL of 1.0 N hydrochloric acid VS into

the Test Preparation while continuing to stir with the Mag-

netic Stirrer for 10 minutes, accurately timed, after the addi-

tion of the acid. Discontinue stirring briefly, and without

delay remove any gum base from the beaker using a long

needle. Promptly rinse the needle with 20 mL of water, col-

lecting the washing in the beaker, and resume stirring for 5

minutes, accurately timed, then begin to titrate immedi-

ately, and in a period not to exceed an additional 5 min-

utes, titrate the excess hydrochloric acid with 0.5 N sodium

hydroxide VS to attain a stable (for 10 to 15 seconds) pH of

Fig. 1. Apparatus for Alginates Assay

SYSTEM SUITABILITY

Using D-glucuronolactone as the standard, proceed as di-

rected for Procedure, but do not perform the preboiling

*This type of tubing is commonly referred to as Tygon tubing. This note is

added for clarity and it does not constitute USP’s endorsement of this

product.

154?311? Alginates Assay / Chemical Tests USP 35

steps. The system is suitable if the following criteria are met:

(1) a blank determination results in a net titration value, C,?341? ANTIMICROBIAL AGENTS—between 0.02 and 0.06 mEq, calculated as follows:CONTENT

A b –

B b

in which A b is the number of mEq of 0.25 N sodium hy-An essential component of Injections preserved in multi-droxide in the 25 mL used, and B b is the number of mEq of ple-dose containers is the agent or agents present to reduce 0.1 N hydrochloric acid used in the blank titration; and (2)the hazard of having introduced, in the course of removing the percentage of carbon dioxide, CO2, obtained from the some of the contents, accidental microbial contamination of standard is between 24.2% and 25.7%.the contents remaining. It is a Pharmacopeial requirement

that the presence and amount added of such agent(s) be

declared on the label of the container. The methods pro-PROCEDURE

vided herein for the most commonly used agents are to be

used to demonstrate that the declared agent is present but Unless otherwise directed in the individual monograph,

does not exceed the labeled amount by more than 20% of transfer a specimen of about 250 mg, accurately weighed,

the labeled amount.

into the reaction flask, D, add 50 mL of 0.1 N hydrochloric

The concentration of an antimicrobial preservative added acid, insert several boiling chips, and connect the flask to

to a multiple-dose or single-dose parenteral, otic, nasal, and the reflux condenser, F, using phosphoric acid as a lubri-

ophthalmic preparation may diminish during the shelf life of cant. [N OTE—Stopcock grease may be used for the other

the product. Because it is recognized that the antimicrobial connections.] Connect the nitrogen line to the sidearm of

preservative concentration in a given preparation may de-the flask, and adjust the flow of cooling water to about 2 L

crease during the product’s shelf life, the manufacturer shall per minute.

determine the lowest level at which the preservative is effec-[N OTE—The following preboiling steps, outlined in this

tive, and the product should be so formulated as to assure paragraph, are optional and need only be performed when

that this level is exceeded throughout the product’s shelf the presence of inorganic carbonates is suspected.] Maintain

life. At the time of its manufacture, the product should con-the flow of nitrogen through the apparatus at 90 to 100 mL

tain the declared amount of antimicrobial preservative

per minute. Raise the heating mantle, E, to the flask, heat

(within ±20% to allow for manufacturing and analytical vari-the specimen to boiling, and boil gently for 2 minutes. Turn

ations). The quantitative label statement of the preservative the heat off, lower the mantle, E, and allow to cool for

content is not intended to mean that the labeled quantity is about 10 minutes.

retained during the shelf life of the product; rather, it is a Connect the empty gas washing bottle assembly, J, and

statement of the amount added, within process limits, and sweep the system with nitrogen at a rate of 90 to 100 mL

which is not exceeded by more than 20%. An example of per minute for 5 minutes. Reduce the nitrogen flow to 60

such a label statement is “____(unit) added as preservative.”to 65 mL per minute, add 10 drops of butyl alcohol, 25.0

[N OTE—“____(unit)” would be a number followed by the mL of 0.25 N sodium hydroxide VS, and 50 mL of distilled

unit of measurement, e.g., 0.015 mg per mL or 0.1%.] water into the bottle, rinsing down the inside of the gas

The most commonly used agents include the two washing bottle, and replace the cap. Detach the rubber fit-

mercurials, phenylmercuric nitrate and thimerosal and the ting, C, from sidearm, and add 46 mL of hydrochloric acid

four homologous esters of p-hydroxybenzoic acid, phenol, through the sidearm of the boiling flask. Reattach the nitro-

benzyl alcohol, and chlorobutanol. The methods for the first gen line, raise the heating mantle, and heat the reaction

two named are polarographic, while quantitative gas chro-mixture to boiling. After 2 hours of boiling, increase the

matography is employed in the determination of the other nitrogen flow to 90 to 100 mL per minute, discontinue the

agents.

heating, and lower the mantle. Allow to cool for 10 min-

utes. Disconnect, and disassemble the gas washing bottle.

Using a directed stream of distilled water, thoroughly rinse GENERAL GAS CHROMATOGRAPHIC

all parts of the bubbling tube and cap, collecting the wash-METHOD

ings in the gas washing bottle. Use nitrogen to gently force

all water out of the bubbling tube. To the bottle immedi-

The general procedures set forth in the following

ately add 10 mL of 10% barium chloride solution and a

paragraphs are applicable to the quantitative determination stirring bar. Insert a tight stopper, and stir gently for 1 min-

of benzyl alcohol, chlorobutanol, phenol, and the methyl, ute. Allow to stand for at least 5 minutes. Add three drops

ethyl, propyl, and butyl esters of p-hydroxybenzoic acid, the of phenolphthalein TS, and titrate with 0.1 N hydrochloric

latter being treated as a group, the individual members of acid VS. Perform a blank determination (see Residual Titra-

which, if present, are capable of separate determination. tions under Titrimetry ?541?). Calculate the percentage of

Prepare the Internal Standard Solution and the Standard Prep-carbon dioxide, CO2, by the formula:

aration for each agent as directed individually below. Unless

otherwise directed below, prepare the Test Preparation from 2200[(A ? B) ? C]/(1000W)(1 ? D)

accurately measured portions of the Internal Standard Solu-

tion and the sample under test, of such size that the con-

in which A is the number of mEq of 0.25 N sodium hydrox-

centration of the agent and the composition of the solvent ide in the 25 mL used; B is the number of mEq of 0.1 N

correspond closely to the concentration and composition of hydrochloric acid used for the titration of the sample or the

the Standard Preparation. Suggested operating parameters of standard; C is the net titration value calculated in the blank

the gas chromatograph apparatus are given in the accom-determination; W is the weight, in g, of the sample or the

panying table, the carrier gas being helium or nitrogen, and standard taken; and D is the percentage expressed as a dec-

the detector being the flame-ionization type.

imal (1 decimal place), obtained in the test for Loss on dry-

ing for the sample or for the standard.

Benzyl Alcohol

Internal Standard Solution—Dissolve about 380 mg of

phenol in 10 mL of methanol contained in a 200-mL volu-

metric flask. Add water to volume, and mix.