Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 44)

Introduction:Surfactants can be classified into cationic, anionic and nonionic ones. Benzalkonium chlorides are cationic surfectants and being widely used as a disinfectant and germicide using their strong protein-denaturing action. Especially in hospitals, 10 % solution of benzalkonium chloride mixture is being usually used; it is diluted to 0.05–0.1 % solution to be used for various types of disinfection. The drugs are contained in gargles and preservative solutions for contact lenses. Fatal benzalkonium chloride poisoning cases, in which the 10 % solution had been ingested, were reported [1, 2]; it can be regarded as one of the most important poisons...
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Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 44) 5.2II.5.2 Benzalkonium chlorides by Kazuhiro Koyama and Yoko ShimazuIntroductionSurfactants can be classified into cationic, anionic and nonionic ones. Benzalkonium chloridesare cationic surfectants and being widely used as a disinfectant and germicide using theirstrong protein-denaturing action. Especially in hospitals, 10 % solution of benzalkonium chlo-ride mixture is being usually used; it is diluted to 0.05–0.1 % solution to be used for varioustypes of disinfection. The drugs are contained in gargles and preservative solutions for contactlenses. Fatal benzalkonium chloride poisoning cases, in which the 10 % solution had been ingested,were reported [1, 2]; it can be regarded as one of the most important poisons in daily necessities.As poisoning symptoms, a pungent sense of the oral mucous membranes, sore throat, cyanosis,convulsion and coma can be mentioned [3, 4]. Benzalkonium chlorides are the mixture of multiple analogous compounds. To measurethe concentration, it is necessary to combine concentrations of each component. The quater-nary ammonium salt benzalkonium chlorides can be expressed as [C6H5CH2N(CH3)2R]Cl,where R is the mixture of C8H17-C18H37. In most cases, the major R’s are C12H25(C12), C14H29(C14)and C16H33(C16); especially according to the National Formulary XVI, C12, C14 and C12 + C14count more than 40, 20 and 70 %, respectively [5]. Therefore, upon analysis of benzalkoniumchlorides, it seems necessary to measure at least the C12 and C14 compounds ( > Figure 2.1).⊡ Figure 2.1Structures of main components of benzalkonium chlorides. Benzalkonium chlorides are a mixtureof quaternary ammonium salts showing the structures of [C6H5CH2N(CH3)2R]Cl, where R is amixture of C8H17–C18H37. However, main structures of R are C12H25(C12), C14H29(C14) and C16H33(C16);C12 40%, C14 20 %, and C12 plus C14 70 % [5].© Springer-Verlag Berlin Heidelberg 2005408 Benzalkonium chlorides In this chapter, a method for wide-bore capillary GC/MS analysis of benzalkonium chlo- rides is described and an HPLC method is also mentioned briefly. GC/MS analysis Reagents and their preparation • A 1-mg aliquot each of benzyldimethyldodecylammonium (C12) bromide, benzyldimethyl- tetradecylammonium (C14) chloride and benzyldimethylhexadecylammonium (C16) chlo- ride (all from Sigma, St. Louis, MO, USA) is dissolved in 100 mL methanol in a 100-mL volmetric flask to prepare 10 µg/mL solution separately. • A 4.3-g aliquot of NaOH is dissolved in distilled water to prepare 100 mL solution (1 M NaOH) in a 100-mL volmetric flask. • A 1-mg aliquot of promazine hydrochloride (Sigma) is dissolved in distilled water to pre- pare 100 mL solution (10 µg/mL promazine, internal standard IS) in a 100-mL volmetric flask. GC/MS conditions GC column: SGE BPX35a (30 m × 0.53 mm i. d., film thickness 1.0 µm, Shimadzu GLC Center, Tokyo, Japan). GC/MS conditions; instrument: GCMS-QP 5050 Ancw (Shimadzu Corp., Kyoto, Japan); column (oven) temperature: 100 °C (1.5 min) → 7 °C/min → 200 °C → 5 °C/min → 330 °C (7 min); interface temperature: 280 °C; injection: PTVb splitless high pressure injectionc, initial injection temperature 50 °C (0.01 min) → 250 °C/min → 330 °C (10 min); initial pressure of injection: 200 kPa, 1.5 min; injection volume: 10 µL; split ratio: 10 ; sampling time: 1.9 min; column flow rate: 15 mL/min; MS ionization: EI; scan range ( > Figure 2.2): m/z 50–509; scan interval: 0.5 s [6]. ⊡ Figure 2.2 Total ion chromatogram (TIC) for the authentic benzalkonium chlorides. C12: benzyldimethyl- dodecylammonium; C14: benzyldimethyltetradecylammonium; C16: benzyldimethylhexadecyl- ammonium. GC/MS analysis 409Proceduresi. Liquid-liquid extractioni. A 50-µL volume each of C12, C14 and C16 methanolic solutions is placed in a small test tube, and evaporated to dryness under a stream of nitrogen with warming at 50 °C. To the com- bined residue, 500 µL blank serum is added and mixed well to prepare 1 µg/mL standard solutiond for C12, C 14 and C16 compounds of benzalkonium chlorides.ii. A 500-µL volume each of specimens (serum, gastric juice or urine) and a 500-µL volume of the above standard solution are placed in separate test tubes, followed by the addition of 2 mL ethyl acetate, 500 µL distilled water, 50 µL of 1 M NaOH solution and 50 µL IS solu- tion, respectively.iii. After voltex-mixing (or shaking) for 3 min, each tube ...