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Arzneimittelforschung 2009; 59(1): 8-12
DOI: 10.1055/s-0031-1296358
Contraceptives
Editio Cantor Verlag Aulendorf (Germany)

Determination of Methyl p-Hydroxy-benzoate, the Metabolite of the Candidate Vaginal Contraceptive Drug 4߰-Carbomethoxyphenyl 4-Guanidinobenzoate Mesylate, in Rabbit Plasma: Application of a rapid and sensitive liquid chromatography-tandem mass spectrometry method

Yin Li
1   Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, (The People’s Republic of China)
,
Zhang Zhengxing
1   Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, (The People’s Republic of China)
,
Hang Taijun
1   Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, (The People’s Republic of China)
› Author Affiliations
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Publication History

Publication Date:
14 December 2011 (online)

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Abstract

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of methyl p-hydroxybenzoate (CAS 99-76-3), the metabolite of the candidate vaginal contraceptive drug 4′-carbomethoxyphenyl 4-guanidinobenzoate mesylate (4′-CMGB) in rabbit plasma. The samples were prepared by liquid-liquid extraction with ethyl acetate after spiking with the internal standard, ethyl p-hydroxybenzoate (PHBA-Et). Chromatographic separation was achieved on a C18 column (4.6 mm × 150 mm, 5 µm) with a mobile phase composition of methanol-water (55:45, v/v) delivered at 1.0 ml/min. LC-MS/MS analysis was carried out on a LC-triple-quadrupole mass spectrometer using atmospheric pressure chemical ionization (APCI) and negative multiple reaction monitoring (MRM). Ions monitored were m/z 151 → 92 for PHBA-Me and m/z 165 → 92 for PHBA-Et with argon at a pressure of 0.8 Pa and collision energy of 32 eV for collision-induced dissociation (CID). The assay was linear over the range of 2.0–100 ng/ml for PHBA-Me. The average recovery was 103.9%. The established method has been applied in a pharmacokinetic study of 4′-CMGB gel in rabbit.

Key words

4′-Carbomethoxyphenyl 4-guanidinobenzoate mesylate, LC-MS/MS, metabolite, pharmacokinetics - CAS 99-76-3 - Contraceptives - Methyl p-hydroxybenzoate
 

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