Hyoung Joon Park

Monitoring of 29 weight loss compounds in foods and dietary supplements by LC-MS/MS

Because of the rapid growth in dietary supplement availability and public concern for weight control, the investigation of foods and various dietary supplements illegally adulterated with weight loss compounds has become increasingly important. A total of 29 weight loss compounds, including sennoside, sibutramine, ephedrine and their analogues, found to be adulterated in foods and dietary supplements were simultaneously examined by LC-MS/MS. The 188 samples were collected between 2009 and 2012 in South Korea, and method validation was performed to determine the adulterants to the weight loss compounds. LODs, LOQs and linearity ranged from 0.03 to 7.5 ng ml−1, from 0.08 to 30.00 ng ml−1, and from 0.990 to 0.999, respectively. The results showed that nine weight loss compounds, namely bisacodyl, desmethylsibutramine, didesmethylsibutramine, ephedrine, fluoxetine, pseudoephedrine, sennoside A, sennoside B and sibutramine, were detected in 62 of all collected samples and were found in order of frequency as follows: sibutramine, 25.7%; sennoside A, 22.9%; sennoside B, 20.0%; fluoxetine, 8.6%; desmethylsibutramine, 7.1%; bisacodyl, ephedrine, and pseudoephedrine, 4.3%; and didesmethylsibutramine, 2.9%. Sibutramine, which was the most frequently found adulterant, ranged in levels from 0.03 to 132.40 mg g−1 (2010), from 0.88 to 76.2 mg g−1 (2011), and from 0.07 to 0.24 mg g−1 (2012). Although the concentrations of most compounds ranged widely, some compounds such as bisacodyl and fluoxetine were found at high concentrations in several samples.

Monitoring of 35 illegally added steroid compounds in foods and dietary supplements.

The adulteration of foods and dietary supplements with steroids has been well attested and has the potential to be dangerous owing to various possible side-effects. Therefore, detecting the presence of steroids in various health food products has become increasingly important. The purpose of this study was to monitor illegally adulterated health food products by applying multiple reaction monitoring techniques to tandem liquid chromatography-mass spectrometry (LC-MS/MS). Various food and supplement samples advertised for the treatment of arthritis, bone ache and joint pain were collected over a 4-year period (2010–13) from local and online Korean sources. The method was validated based on limits of quantification of 0.5–15.0 ng g−1 and recoveries in spiked solid samples of 81–119%. Approximately 30% of the tested samples were identified as having been illicitly adulterated. Six compounds were observed overall, including dexamethasone (45.1%), cotrisone-21-aceteate and prednisone-21-acetate (16.2%), and betamethasone (14.4%), and found in some samples in high concentrations.

LC-ESI-MS/MS analysis of phosphodiesterase-5 inhibitors and their analogues in foods and dietary supplements in Korea

A number of 188 food and dietary supplement samples were collected from 2009 to the first half of 2013 in Korean online and offline stores. A method to identify phosphodiesterase-5 (PDE-5) inhibitors and their analogues using liquid chromatography-electrospray ionisation-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) was validated. Limit of detection and limit of quantitation of liquid-type and solid-type negative samples ranged from 0.05 to 3.33 ng/mL or ng/g and from 0.15 to 10.00 ng/mL or ng/g, respectively. Recoveries ranged from 83% to 112%. Nineteen PDE-5 inhibitors and their analogues were detected, with tadalafil group compounds being the most frequently observed (53.0%), followed by the sildenafil group (42.5%). Tadalafil concentrations ranged from 0.08 to 138.69 mg/g. Compounds were most frequently detected in capsules (in 40 of 80 adulterated samples). To protect public health and food safety, appropriate monitoring of PDE-5 inhibitors and their analogues in foods and dietary supplements is recommended.

Determination of anabolic-androgenic steroid adulterants in counterfeit drugs by UHPLC-MS/MS.

Anabolic-androgenic steroids (AASs) have been illegally used in counterfeit drugs to improve the performance of athletes. In addition, AASs have been used for cosmetic purpose by non-athletes. To determine the presence of 26 AASs, an analysis method using ultra-liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. The validated method was applied to 19 counterfeit drugs collected from the Internet and off-line markets during 2014. Nearly 50% (9/19) of the samples contained one of these 26 AASs. In addition, the concentration ranges of the AASs ranged from 0.09 to 119,228.57 mg/kg in the suspected samples. The determined AASs primarily consisted of testosterone and testosterone 17-propionate (26%) followed by boldenone (21%). These results indicate the adulteration of over-the-counter counterfeit drugs, and the continuous monitoring of counterfeit drugs or dubious dietary supplements containing anabolic steroids is warranted.

Identification of a new tadalafil analogue in an adulterated dietary supplement: trans-Bisprehomotadalafil.

A new tadalafil analogue was identified along with homotadalafil during routine screening of an adulterated dietary supplement using HPLC-DAD. The UV spectrum of this analogue was almost identical with that of tadalafil. This compound was isolated from the supplement by using semi-preparative HPLC and its structure was subsequently elucidated by performing Q-TOF/MS/MS and NMR spectroscopic experiments. The spectral data indicate that this tadalafil analogue is a dimeric compound that consists of an ethylamino group and two pretadalafil moieties. NOE experiments and comparison with (1)H NMR spectra of tadalafil and trans-tadalafil suggested the trans-relationship between the substituents on piperidine rings in the pretadalafil moieties.

Determination of non-opioid analgesics in adulterated food and dietary supplements by LC-MS/MS

Commercially available non-opioid analgesics such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been used to adulterate some foods and dietary supplements. Considering the rapid growth of the dietary supplement market, it is essential to analyse various analgesics used for adulteration over a time period. Acetaminophen and 16 NSAIDs used to adulterate food and dietary supplements were simultaneously determined by LC-MS/MS. The method was validated by determining the coefficient of determinations, limit of quantification and recovery, and samples were analysed for the determination of analgesics. Consequently, acetaminophen, diclofenac, ibuprofen, indomethacin, naproxen and piroxicam were detected in 53 samples (n = 214). Ibuprofen was the most commonly used adulterant, which was detected in a wide concentration range (1.06–233.40 mg g–1) and was present in about one-third of the adulterated samples. Various types of samples, in particular pills and capsules (73.6% of the total positive samples), were found to be adulterated with non-opioid analgesics. Samples containing high concentrations of analgesics can have a deleterious effect on human health, and thus the continued monitoring of adulterated food and dietary supplements is essential to maintain a healthy life.

Determination of Miroestrol and Isomiroestrol From Pueraria mirifica (White Kwao Krua) in Dietary Supplements by LC–MS-MS and LC–Q-Orbitrap/MS

The purpose of this study is to develop LC-MS-MS and LC-Q-Orbitrap/MS method for the analysis of the components of Pueraria mirifica, which are illegal additives in dietary supplements. Blank samples and samples spiked with miroestrol and isomiroestrol were used for the initial development and validation studies. Specificity, linearity, limit of quantification (LOQ), limit of detection (LOD), accuracy, precision, recovery and stability were employed as the validation parameters. The LODs of miroestrol and isomiroestrol were found to be 4.17 and 0.84 ng/mL, respectively, whereas their LOQs were 12.50 and 2.52 ng/mL, respectively. The determination coefficient was over 0.999, intra- and inter-day precisions were 0.8-6.9 and 1.9-9.8%, respectively, and intra and inter-day accuracies were 82.1-103.7 and 85.0-109.7%, respectively. The mean recoveries of the targeted compounds from the dietary supplements ranged from 86.9 to 108.9%. The relative standard deviations (RSDs) for recovery were <5.8%. On the other hand, the RSD of stability was <11.0%. Eight dietary supplements were tested using the newly developed and validated method, out of which six were found to be adulterated samples.

Simultaneous Analysis of Cannabinoid and Synthetic Cannabinoids in Dietary Supplements Using UPLC with UV and UPLC–MS-MS

The primary purpose of this study was to develop and validate a method based on UPLC with UV and UPLC-MS-MS for the simultaneous analysis of different cannabinoids and synthetic cannabinoids in food as well as in herbal and dietary supplements. The limits of detection and quantitation of the method ranged from 0.1 to 0.3 and 0.3 to 0.9 μg/mL by UPLC with UV, respectively. The coefficient of determination was >0.999; the intra- and interday precision of the method were 0.1-3.7 and 0.9-4.1%, respectively. The intra- and interday accuracy were 94.8-103.1 and 98.3-100.9%, respectively. The mean recoveries of nine cannabinoids obtained from tablet samples ranged from 81.1 to 105.4%. The mean extraction recoveries of nine target cannabinoids obtained from various types of samples (tablets, capsules, powders, liquids, cookies and candies) ranged from 82.26 to 112.40%. The relative standard deviation (RSD) of the stability of the prepared sample solutions was <1.80%. Identification and quantification of the nine cannabinoids were accomplished by ion spray UPLC-MS-MS using multiple reaction monitoring. The UPLC-MS-MS method was validated for linearity (R(2) > 0.99); the precision was 0.1-4.0% (intraday) and 0.1-2.8% (interday), and the accuracy was 98.0-103.5% (intraday) and 97.1-103.2% (interday). The mean extraction recoveries of six types of samples were 82.2-114.5% and the RSD of stability was <6.54%, complying with the established international guidelines. The results indicated that the method can be used for rapid and accurate screening of cannabinoids present in food.

A rapid method for the simultaneous determination of 25 anti-hypertensive compounds in dietary supplements using ultra-high-pressure liquid chromatography

ABSTRACT A novel, stable, simple and specific ultra-performance liquid chromatography method with ultraviolet detection (205 nm) for the simultaneous analysis of 25 anti-hypertensive substances was developed. The method was validated according to the International Conference of Harmonisation guidelines with respect to linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ) and stability. From the ultra-performance liquid chromatography results, we identified the LOD and LOQ of solid samples to be 0.20–1.00 and 0.60–3.00 μg ml−1, respectively, while those of liquid samples were 0.30–1.20 and 0.90–3.60 μg ml−1, respectively. The linearity exceeded 0.9999, and the intra- and inter-day precisions were 0.15–6.48% and 0.28–8.67%, respectively. The intra- and inter-day accuracies were 82.25–111.42% and 80.70–115.64%, respectively, and the stability was lower than 12.9% (relative standard deviation). This method was applied to the monitoring of 97 commercially available dietary supplements obtained in Korea, such as pills, soft capsules, hard capsules, liquids, powders and tablets. The proposed method is accurate, precise and of high quality, and can be used for the routine, reproducible analysis and control of 25 anti-hypertensive substances in various dietary supplements. The work presented herein may help to prevent incidents related to food adulteration and restrict the illegal food market.

Isolation and structural identification of a novel minoxidil analogue in an illegal dietary supplement: triaminodil

ABSTRACT A new minoxidil analogue was detected in an illegal dietary supplement advertised as a hair-growth treatment. The analogue was identified using ultra-performance liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil was replaced with a pyrrolidinyl group corresponding to a molecular formula of C8H13N5O. The new analogue has been named triaminodil. As this is the first report of the compound, there are no chemical, toxicology or pharmacological data available. Graphical Abstract