高灵敏度LC/MS/MS法同时测定人血浆中麻黄碱和氯苯那敏

麻黄碱是存在于草麻黄和木贼麻黄等植物中的生物碱,属拟肾上腺素类药物,包括互为差向异构体的麻黄碱和伪麻黄碱两种活性不同的成分;氯苯那敏为丙胺类组胺H1-受体拮抗剂,作用较强,用量少,中枢抑制作用小,为常用抗过敏药,临床上可用于缓解各种感冒症状,与麻黄碱联合应用,用于缓解支气管哮喘与慢性喘息性支气管炎所致支气管痉挛.

Simultaneous determination of ephedrine and chlorpheniramine in human plasma by a highly sensitive liquid chromatography-tandem mass spectrometric method

AIM: To develop and validate a liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the simultaneous quantification of ephedrine and chlorpheniramine in human plasma after oral administration of a compound preparation. METHODS: The analytes and the internal standard, diphenhydramine, were isolated from plasma by protein precipitation with methanol, then chromatographied on a Zorbax SB-C18 column (150 mm x 4.6 mm ID) using a mobile phase consisted of methanol-water-formic acid (80: 20: 0.5, v/v), at a flow rate of 0.5 mL x min(-1). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor to produce ion combinations of m/z 166-->115, m/z 275-->230 and m/z 256-->167 were used to quantify ephedrine, chlorpheniramine and the internal standard, respectively. Results The linear concentration ranges of the calibration curves for ephedrine and chlorpheniramine were 0.50 - 200 microg x L(-1) and 0.050 - 20.0 microg x L(-1), respectively. The lower limits of quantification were 0. 50 microg x L(-1) for ephedrine and 0.050 microg x L(-1) for chlorpheniramine, individually. The intra- and inter-day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 9.3% for both ephedrine and chlorpheniramine. The inter-day accuracy (RE) was within +/- 3.4% for the analytes. Each sample was chromatographied within 3.3 min. The method was successfully used in pharmacokinetics study of ephedrine and chlorpheniramine in human plasma after oral administration of a compound preparation containing 5 mg ephedrine hydrochloride, 1 mg chlorpheniramine maleate, 50 mg phenytoin, 12.5 mg theophylline, 12.5 mg theobromine and 7.5 mg caffeine. No interaction among the six components was observed on their pharmacokinetic parameters. CONCLUSION: The method was proved to be highly sensitive, selective, and suitable for pharmacokinetics investigations of different compound preparations containing low dosage of both ephedrine and chlorpheniramine.