Determination of sidenafil concentration in human plasma by LC-MS/MS with internal standard method

Abstract

Abstract: AIM: To establish an LC-MS/MS method for determining the concentration of sildenafil in human plasma.METHODS: Diazepam was used as internal standard,the plasma samples extracted by MTBE were separated on a Waters XTerra MS C₁₈ column (150 mm×2.1 mm, 5 μm) with mobile phase contained methanol and 10 mmol/L Ammonium acetate( 85∶15, V/V) at flow rate of 0.30 mL/min. The electrospray ionization (ESI source) in positive ion multiple reaction monitoring (MRM) were used for scanning analysis, then, sildenafil and diazepam ion selective channels were: m/z 475.3→58.1 and 285.5→154.0, respectively.RESULTS: The linear range for sildenafil was 1.50-765.90 ng/mL. The lower limit of quantitation was 1.50 ng/mL, and the relative standard deviation of intra-day and inter-day were less than 15%.CONCLUSION: The estalished method is suitable for clinical pharmacokinetic study of sildenafil.

Key words: LC-MS/MS, Sildenafil, Internal standard

CLC Number:

R969.1

DENG Xiao-lan, TAN Zhi-rong, CHEN Yao, LI Hui, WANG Yi-cheng, HUANG Qi, OUYANG Dong-sheng. Determination of sidenafil concentration in human plasma by LC-MS/MS with internal standard method[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(11): 1272-1276.

References

[1] 田平林.选择性环鸟苷酸-磷酸二酯酶5抑制药的研究进展[J].医药导报, 2003, 22 ( s1 ) : 50-51.
[2] Al-Ghazawi M, Tutunji M, Aburuz S. Simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma by high-performance liquid chromatography method using electrochemical detection with application to a pharmacokinetic study[J]. J Pharm Biomed Anal, 2007, 43 ( 2 ) : 613 - 618.
[3] Pistos C, Papoutsis I, Dona A, et al. Off-line HPLC method combined to LC-MS for the determination of sildenafil and its active metabolite in post-mortem human blood according to confirmation criteria [J]. Forensic Sci Int, 2008, 178 (2/3) : 192- 198.
[4] Wang Y, Wang J, Cui Y, et al. Liquid chromatographic-tandem mass spectrometric method for the quantitation of sildenafil in human plasma [J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2005, 828 ( 1/2 ) : 118 - 121.
[5] Lewis RJ, Johnson RD, Blank CL. Quantitative determination of sildenafil (Viagra) and its metabolite (UK-103,320) in fluid and tissue specimens obtained from six aviation fatalities [J]. J Anal Toxicol, 2006, 30 ( 1 ) : 14 - 20.
[6] Sheu MT, Wu AB, Yeh GC. Development of a liquid chromatographic method for bioanalytical applications with sildenafil [J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2003, 791 (1/2) : 255 - 262.
[7] Vos RM, Chahbouni A, Sinjewel A. Quantitative analysis of sildenafil and desmethylsildenafil in human serum by liquid chromatography-mass spectrometry with minimal sample pretreatment [J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2008, 876 (2) : 283-287.
[8] Tracqui A, Ludes B. HPLC-MS for the determination of sildenafil citrate (Viagra) in biological fluids. Application to the salivary excretion of sildenafil after oral intake [J]. J Anal Toxicol, 2003, 27 ( 2 ) : 88 - 94 .
[9] 杨士云, 袁增平, 乔静. 全血中西地那非的HPLC分析[J].中国法医学杂志, 2009, 24 (6) : 392 - 393.
[10] Alkharfy KM. Simple and sensitive LC-ESI-MS method for the quantitation of sildenafil in plasma samples [J].J Sep Sci, 2009, 32 ( 22 ) : 3866-3870.

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