Reliable screening and confirmation of 156 multi-class illegal adulterants in dietary supplements based on extracted common ion chromatograms by ultra-high-performance liquid chromatography-quadrupole/time of flight-mass spectrometry.

An analytical method for the reliable screening and confirmation of 156 illegal drugs (58 erectile dysfunction drugs, 49 synthetic steroids, 26 anabolic steroids, and 23 anti-histamine drugs) in supplementary diets using ultra-high-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF-MS) was developed. Various types of supplements (liquid, capsule, powder, pill and tablet) with complicated matrices were pretreated by simple liquid-liquid extraction. The wide scope of 156 target compounds was effectively determined within 15min in the positive ion mode, detecting the compounds at a sub-ppb level. Their MS/MS spectra were preferentially investigated to find diagnostic common ions according to the structural similarity of diverse adulterants. For the rapid screening of multiple classes of the target adulterants, extracted common ion chromatograms (ECICs) based on specific fragments of similar molecular moieties were attempted. A database including the elemental compositions, retention times, and MS/MS spectra was built for the confirmation of adulterants. The established method was validated in terms of the linearity, limits of detection (LOD), precision, and accuracy. The linear correlation coefficient and limit of detection ranged from 0.9880 to 1 and from 0.02 to 16.04ng/mL, respectively. The precision and accuracy of intra- and inter-day experiments for the spiked samples at the range of 0.2 and 16.0ng/mL were from 0.16 to 13.50% and 0.19-11.48%, respectively, with relative standard deviation. Mean recoveries ranged from 81.6 to 124.7%, and relative standard deviation was less than 9.20%. The screening and confirmation method demonstrated the usefulness of UHPLC-Q/TOF-MS combined with ECICs as a promising approach for the analysis of multi-class adulterants. Finally, the established method was successfully applied for the monitoring of several types of dietary supplements in routine analysis.

[1]  B. Ma,et al.  Rapid analysis of tadalafil in human blood plasma and seminal plasma by liquid chromatography/tandem mass spectrometry. , 2013, Journal of pharmaceutical and biomedical analysis.

[2]  R. Schwartz,et al.  Adverse effects of topical glucocorticosteroids. , 2006, Journal of the American Academy of Dermatology.

[3]  J. H. Lee,et al.  Determination of anabolic-androgenic steroid adulterants in counterfeit drugs by UHPLC-MS/MS. , 2015, Journal of pharmaceutical and biomedical analysis.

[4]  J. S. Barnes,et al.  Differentiating Isobaric Steroid Hormone Metabolites Using Multi-Stage Tandem Mass Spectrometry , 2013, Journal of The American Society for Mass Spectrometry.

[5]  M. Popławska,et al.  Application of high-performance liquid chromatography with charged aerosol detection for universal quantitation of undeclared phosphodiesterase-5 inhibitors in herbal dietary supplements. , 2013, Journal of pharmaceutical and biomedical analysis.

[6]  J. Zweigenbaum,et al.  Characterization and quantitation of yohimbine and its analogs in botanicals and dietary supplements using LC/QTOF-MS and LC/QQQ-MS for determination of the presence of bark extract and yohimbine adulteration. , 2015, Journal of AOAC International.

[7]  Ji Won Kim,et al.  Simultaneous determination of 38 phosphodiestrase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography-electrospray ionization-tandem mass spectrometry. , 2013, Journal of pharmaceutical and biomedical analysis.

[8]  J. McVeigh,et al.  Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health. , 2015, Drug testing and analysis.

[9]  Ó. Pozo,et al.  Current LC–MS methods and procedures applied to the identification of new steroid metabolites , 2016, The Journal of Steroid Biochemistry and Molecular Biology.

[10]  F. Song,et al.  Screening for multiple phosphodiesterase type 5 inhibitor drugs in dietary supplement materials by flow injection mass spectrometry and their quantification by liquid chromatography tandem mass spectrometry. , 2012, Journal of pharmaceutical and biomedical analysis.

[11]  Sara Rubinelli,et al.  “Save 30% if you buy today”. Online pharmacies and the enhancement of peripheral thinking in consumers , 2010, Pharmacoepidemiology and drug safety.

[12]  Lukáš Václavík,et al.  Mass spectrometric analysis of pharmaceutical adulterants in products labeled as botanical dietary supplements or herbal remedies: a review , 2014, Analytical and Bioanalytical Chemistry.

[13]  S. Arver,et al.  Counterfeit phosphodiesterase type 5 inhibitors pose significant safety risks , 2010, International journal of clinical practice.

[14]  V. Andreu,et al.  Analysis of psychoactive substances in water by information dependent acquisition on a hybrid quadrupole time-of-flight mass spectrometer. , 2016, Journal of chromatography. A.

[15]  Caisheng Wu,et al.  Simultaneous screening and determination of 18 illegal adulterants in herbal medicines and health foods for male sexual potency by ultra-fast liquid chromatography-electrospray ionization tandem mass spectrometry. , 2012, Journal of separation science.

[16]  R. Heywood,et al.  Toxicity of venalot (a mixture of coumarin and troxerutin) in the baboon. , 1983, Toxicology letters.

[17]  R. Patterson,et al.  Lifestyle illicit drug seizures: a routine ESI-LC-MS method for the identification of sildenafil and vardenafil. , 2012, Forensic Science International.

[18]  D. Barceló,et al.  Structure elucidation of phototransformation products of unapproved analogs of the erectile dysfunction drug sildenafil in artificial freshwater with UPLC-Q Exactive-MS. , 2014, Journal of mass spectrometry : JMS.

[19]  Ji Yeon Choi,et al.  LC–MS/MS monitoring of 22 illegal antihistamine compounds in health food products from the Korean market , 2015, Journal of the Korean Society for Applied Biological Chemistry.

[20]  Hyung Joo Kim,et al.  Monitoring of 35 illegally added steroid compounds in foods and dietary supplements , 2014, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[21]  I. Goldstein,et al.  Internet-ordered viagra (sildenafil citrate) is rarely genuine. , 2012, The journal of sexual medicine.

[22]  E. Castrignanò,et al.  Determination of anabolic agents in dietary supplements by liquid chromatography-high-resolution mass spectrometry , 2015, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[23]  C. Meston,et al.  Recreational use of erectile dysfunction medications and its adverse effects on erectile function in young healthy men: the mediating role of confidence in erectile ability. , 2012, The journal of sexual medicine.

[24]  Elisa A Nickum,et al.  Isolation and structural characterization of a new tadalafil analog (2-hydroxyethylnortadalafil) found in a dietary supplement. , 2015, Journal of pharmaceutical and biomedical analysis.

[25]  C. Spiliopoulou,et al.  Adverse effects of anabolic steroids in athletes. A constant threat. , 2005, Toxicology letters.

[26]  Bong Jin Lee,et al.  A novel approach to simultaneous screening and confirmation of regulated pharmaceutical compounds in dietary supplements by LC/MS/MS with an information-dependent acquisition method , 2011, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[27]  Jaeick Lee,et al.  Simultaneous analysis of 210 prohibited substances in human urine by ultrafast liquid chromatography/tandem mass spectrometry in doping control. , 2015, Rapid communications in mass spectrometry : RCM.

[28]  B. Le Bizec,et al.  Ultra high performance liquid chromatography/tandem mass spectrometry based identification of steroid esters in serum and plasma: an efficient strategy to detect natural steroids abuse in breeding and racing animals. , 2013, Journal of chromatography. A.

[29]  K. Chung,et al.  Development of a comprehensive spectral library of sildenafil and related active analogues using LC-QTOF-MS and its application for screening counterfeit pharmaceuticals. , 2015, Forensic science international.

[30]  P. Di Martino,et al.  Characterization of Sildenafil analogs by MS/MS and NMR: a guidance for detection and structure elucidation of phosphodiesterase-5 inhibitors. , 2014, Journal of pharmaceutical and biomedical analysis.

[31]  Bin Guo,et al.  Wide-Scope Screening of Illegal Adulterants in Dietary and Herbal Supplements via Rapid Polarity-Switching and Multistage Accurate Mass Confirmation Using an LC-IT/TOF Hybrid Instrument. , 2015, Journal of agricultural and food chemistry.

[32]  Lubertus Bijlsma,et al.  LC-QTOF MS screening of more than 1,000 licit and illicit drugs and their metabolites in wastewater and surface waters from the area of Bogotá, Colombia , 2015, Analytical and Bioanalytical Chemistry.

[33]  R. Leurs,et al.  H1‐antihistamines: inverse agonism, anti‐inflammatory actions and cardiac effects , 2002, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[34]  K. Waldron,et al.  A rapid, quantitative liquid chromatography-mass spectrometry screening method for 71 active and 11 natural erectile dysfunction ingredients present in potentially adulterated or counterfeit products. , 2014, Journal of chromatography. A.