Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 33)

Introduction:Diphenylmethane antihistaminics are being widely used for treatments of allergy, motion (travel) sickness and cold. They are also being sold as over-the-counter drugs. The structures of principal drugs of this group are shown in Figure 1.1. They are being analyzed by GC [1–6] and HPLC [7–13]. In this chapter, a GC method for simultaneous analysis of diphenylmethane antihistaminics and also HPLC methods for some representative drugs of this group are presented.
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Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 33) 4.1II.4.1 Diphenylmethane antihistaminics by Yoko Hieda and Kojiro KimuraIntroductionDiphenylmethane antihistaminics are being widely used for treatments of allergy, motion(travel) sickness and cold. They are also being sold as over-the-counter drugs. The structures ofprincipal drugs of this group are shown in > Figure 1.1. They are being analyzed by GC [1–6]and HPLC [7–13]. In this chapter, a GC method for simultaneous analysis of diphenylmethaneantihistaminics and also HPLC methods for some representative drugs of this group are pre-sented.Simultaneous analysis by GC [4]Reagents and their preparation• Diphenhydramine hydrochloride, diphenylpyraline hydrochloride, phenyltoloxamine citrate, orphenadrine hydrochloride, benactyzine hydrochloride, doxylamine succinate, carbinoxamine maleate, chlorpheniramine maleate, triprolidine hydrochloride, homo- chlorcyclizine dihydrochloride, hydroxyzine dihydrochloride, clemastine fumarate and meclizine dihydrochloride can be purchased from Sigma (St. Louis, MO, USA). Pure powder of terodiline hydrochloride and piperilate hydrochloride was donated by Kissei Pharmaceutical Co., Ltd., Nagano, Japan and Nippon Shinyaku Co., Ltd., Kyoto, Japan, respectively. Sep-Pak C18 cartridges (classic type) were purchased from Waters (Milford, MA, USA). Other common chemicals were of the highest purity commercially available.• Care should be taken for that all of the above 15 kinds of drugs are in the salt forms. All compounds (5-mg each as the weight of its free base) are altogether dissolved in methanol to prepare 10 mL solution; a 10-µL volume of the mixture solution is spiked into 1 mL of whole blood or urine. One of the 15 drugs is selected for use as internal standard (IS).• Chloroform/methanol (9:1) and distilled water, 100–200 mL each, are prepared.• 0.5 M NaHCO3 solution: a 4.2-g aliquot of NaHCO3 is dissolved in distilled water to pre- pare 100 mL solution.GC conditionsGC columna: DB-1 (15 m × 0.32 mm i. d., film thickness 1.0 µm), DB-17 (15 m × 0.32 mmi. d., film thickness 0.25 µm) both obtained from J & W Scientific (Folsom, CA, USA).© Springer-Verlag Berlin Heidelberg 2005316 Diphenylmethane antihistaminics ⊡ Figure 1.1 Structures of principal diphenylmethane antihistaminics. GC conditions: an HP 5890 Series II gas chromatographb (Agilent Technologies, Palo Alto, CA, USA); detector: FID; column temperatures: 160 °C (1 min) →5 °C/min →290 °C for the DB-1 column, and 160 °C (1 min) →5 °C/min →280 °C for the DB-17 column; injection tem- perature: 240 °C; detection temperature: 280 °C; carrier gas: He; its flow rate: 3 mL/min; a 1-µL aliquot of sample solution is injected into GC in the splitless mode (1 min), followed by the split mode at 160 °C of oven temperature. Simultaneous analysis by GC 317Procedurei. A 10-mL volume of methanol and 10 mL distilled water are passed through a Sep-Pak C18 cartridge c for its activation.ii. A 10-µL aliquot of methanolic solution of a suitable ISd (in case of simultaneous analysis of spiked drugs, 5 µg each in the 10 µL solution) is added to 1 mL whole blood, and mixed well with 9 mL distilled water for complete hemolysis. To this mixture, 5 mL of 0.5 M NaH- CO3 solution is added to make it slightly alkaline. To 1-mL volume of a urine specimen, a 10-µL aliquot of the IS solution, 4 mL distilled water and 5 mL of 0.5 M NaHCO3 solution are added.iii. Either mixture of whole blood or urine specimen is poured e into the activated cartridge with a flow rate not faster than 5 mL/min using a 10-mL volume glass syringe.iv. The cartridge is washed with 10 mL distilled water, and the target compounds are slowly eluted with 3 mL of chloroform/methanol (9:1) into 4-mL volume glass vial.v. A small amount of the upper aqueous phase of the eluate is carefully removed with a Pas- teur pipette; the lower organic phase is evaporated to dryness under a stream of nitrogen. The residue is dissolved in 100 µL methanol, and a 1-µL aliquot of it is injected into GC. For quantitation, the peak area ratio of a target compound to IS is obtained.vi. For quantitative analysis, a 10-µL of IS solution and one of various concentrations of a target compound are added to 1 mL of blank whole blood or urine obtained from healthy subjects; at least 4 vials containing different concentrations of the compound should be prepared. These vials are processed according to the above procedure and analyzed ...