Quaternary amines assay

Non-aqueous titration with acetous perchloric acid is used in the pharmacopoeial assays of adrenaline, metronidazole, codeine, chlorhexidine acetate, chlorpromazine.HCl, amitriptyline.HCl, propranolol.HCl, lignocaine.HCl and quaternary amine salts such as neostigmine bromide and pancuronium bromide. 

A colorimetric method which takes advantage of the quaternary amine moiety in levallorphan tartrate is the extraction of the ion pair formed with bromocresol green. The levallorphan tartrate in injectables is assayed by this method (9). The complex is formed in an aqueous... 

Homopolymers, as well as random and block copolymers with PDMS, were created by a combination of polycondensation and anionic ring-opening polymerization. To convert the chlor-opropyl side groups into quaternary ammoniums, the polymer was first treated with lithium bromide to replace the chlorine with bromine. The polymer was dissolved with (3-hydroxypro-pyl)dimethylamine to create the amphiphilic quaternary amine-functionalized polymer. Bactericidal assays of statistical and block copolymers gave MIC values of 6-25 pgmr against E. coli and S. aureus, with somewhat better activity against S. aureus. 

Quaternary amines may be assayed by titration with an anionic surfactant by the potentio-metric or two-phase procedures described in Chapter 16. The ISO procedure specifies titration with sodium dodecyl sulfate, which is available in high purity (7). Sodium tetraphenylborate may also be used if potassium and ammonium ions are absent. Other approaches to assay are based on acid-base titration or quantification of the anion associated with the quaternary. 

Quaternary amine salts may be titrated with acid by conventional nonaqueous procedures. To be precise, the anion associated with the quaternary is titrated. In the case of halides, mercuric acetate is added to replace free halide ion with easily titratable acetate ion [see Section III] (8,9). Such methods are suitable for analysis of pure samples, which do not contain other salts. A more specific assay of cationic surfactants is the two-phase titration with an anionic surfactant, described in Chapter 16. 

The ester group positional isomer (134) is less potent and less active than arecoline in the guinea pig ileum assay (176), and the N,N-dimethyl quaternary derivative of (134) is slightly more potent than the tertiary amine. 

Water soluble 7-substituted quaternary anunonium salt derivatives of 10,11 -(methylenedioxy) - and 10,11 -(ethylenedioxy)-(20S)-camptothecin 216 (Figure 9) are synthesized via the Friedlander reaction followed by nucleophilic displacement with an aromatic amine. All are more potent than camptothecin in the in vitro cleavable complex assay (96JME713). 

The compendial method for assay of benzalkonium chloride is based upon reversal of the quaternization reaction. The compound is reacted with Nal, the benzyl iodide and tertiary amine are removed by extraction, and the iodide consumed is determined by titration with KIO3 (9). The alkyl chain length distribution is determined by HPLC. Other tests for characterization of benzalkonium salts are similar to those performed on alkyl quaternaries. These salts are also readily determined by two-phase or potentiometric titration with an anionic surfactant. 

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