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Article

Rapid Screening and Identification of Illegally Adulterated PDE-5 Inhibitors in Health Wines by UPLC-TOF-MS

by
Xiaobei Huang
1,*,
Ben Li
1,
Hui Wang
1,
Lixia Yang
1,
Zi Yi
1,
Yuli Fu
2 and
Yun Du
3
1
Changsha Institute for Food and Drug Control, National Alcohol Products Quality Supervision and Inspection Center, Changsha 410013, China
2
Key Laboratory of the Assembly and Application of Organic Functional Molecules, Hunan Normal University, Changsha 410081, China
3
Changsha Center for Diseases Prevention and Control, Changsha 410004, China
*
Author to whom correspondence should be addressed.
Processes 2025, 13(12), 3800; https://doi.org/10.3390/pr13123800
Submission received: 31 October 2025 / Revised: 19 November 2025 / Accepted: 22 November 2025 / Published: 25 November 2025
(This article belongs to the Section Food Process Engineering)
Browse Figures
Versions Notes

Abstract

Health wines are alcoholic beverages produced by infusing traditional liquors or rice wines with natural, medicinal, and food-safe ingredients. However, to accelerate efficacy, some manufacturers illegally adulterate health wines with phosphodiesterase type 5 (PDE-5) inhibitors, which may cause severe adverse effects. This study developed a method based on ultra-high-performance liquid chromatography–time-of-flight mass spectrometry (UPLC–TOF/MS) for the rapid screening and identification of 68 PDE-5 inhibitors illegally added to health wines. After optimizing the sample preparation procedure, chromatographic conditions, mass spectrometric parameters, and primary and secondary mass spectra of the 68 PDE-5 inhibitors were acquired as reference standards. Retention times and mass spectral data were imported into the Personal Compound Database and Library, establishing a high-resolution screening database with matched drug names, molecular formulas, and accurate molecular weights. A quantitative method was validated using 11 commonly adulterated compounds, including sildenafil. The response was highly linear (r ≥ 0.9988; 0.8–400 μg/L) with low detection limits (0.2–1.0 μg/L). The average spiked recoveries were 71.2–104.1%, with relative standard deviations of ≤10.1%. Among 59 commercial health wine samples, three batches tested positive for PDE-5 inhibitors (detection rate: 5.1%). The proposed method can assist market surveillance even when reference standards are unavailable for all compounds.

1. Introduction

Health wines, alcoholic beverages produced by infusing traditional liquors or rice wines with natural, medicinal, and food-safe ingredients, have been widely consumed since historical times in China due to their perceived health benefits [1,2,3,4]. The rising public focus on health wellness has steadily expanded the market for these products. However, to achieve a rapid effect, some manufacturers illegally adulterate these products with phosphodiesterase type 5 (PDE-5) inhibitors, such as sildenafil, tadalafil, and vardenafil [5,6,7,8,9], which are licitly prescribed for the treatment of erectile dysfunction. These drugs are administered under strict medical supervision as overdose or concomitant administration with nitrates can induce severe adverse effects, including hypotension, myocardial infarction, and even life-threatening cardiovascular events [10,11,12,13].
At present, PDE-5 inhibitors in foods are detected using high-performance liquid chromatography (HPLC) [14], gas chromatography–mass spectrometry (GC-MS) [15], and liquid chromatography–tandem mass spectrometry (LC–MS/MS) [16,17,18,19,20]. Although these techniques are reliable, they predominantly rely on reference standards for targeted analysis, and their screening ability deteriorates when analyzing unknown or structurally modified analogs, which are increasingly used to evade detection. Furthermore, these methods often involve lengthy analysis durations, incur high operational costs, and involve complex procedures, limiting their suitability for high-throughput screening and market surveillance.
As an alternative technique, ultra-high-performance LC coupled with time-of-flight MS (UPLC–TOF/MS) offers high resolution, accurate mass measurement, and rapid scanning capability, allowing the establishment of comprehensive spectral libraries and the reliable identification of compounds even in the absence of reference standards [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]. Despite its potential, UPLC–TOF/MS has been limitedly applied to the screening of PDE-5 inhibitors in health wines. Many existing studies focused on a narrow range of target analytes; hence, systematic research on comprehensive database building and subsequent risk assessment of real market samples is currently lacking [43].
To fill this knowledge gap, we developed a high-resolution rapid screening method for a wide spectrum of PDE-5 inhibitors present in health wines. Based on a review of national surveillance data and recent literature, we first identified 68 high-risk PDE-5 inhibitors as target analytes [44,45,46]. After establishing the UPLC–TOF/MS method, we optimized the sample preparation process and instrumental parameters to create a robust accurate mass spectral library. The practical applicability of the library was validated via the risk screening and assessment of 59 commercial health wine samples collected from a market in Hunan Province, China.
The quantitative method was developed and validated specifically for the direct determination of these compounds as illegally added substances in health wine products. The aim was to provide a reliable means for regulatory authorities to quantify the extent of adulteration in suspect samples, which is crucial for risk assessment and enforcement actions.
Overall, the proposed strategy enables efficient and reliable nontargeted screening and regulatory control of illegal adulteration in health wines.

2. Materials and Methods

2.1. Chemicals, Reagents, and Instruments

In this study, 68 PDE-5 inhibitor reference standards (purity ≥ 98%), including sildenafil, tadalafil, and vardenafil, were purchased from Anpel Laboratory Technologies (Shanghai, China). HPLC-grade methanol and acetonitrile were obtained from Merck KGaA (Darmstadt, Germany). Ammonium acetate and formic acid (analytical grade) were procured from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Ultrapure water was prepared using a Direct-Q® 8 UV-R water purification system (Millipore, Bedford, MA, USA).
The instruments included an Agilent 6545 time-of-flight mass spectrometer (Agilent Technologies, Santa Clara, CA, USA) coupled with an Agilent 1290 high-performance liquid chromatography system (Agilent Technologies, Santa Clara, CA, USA), a numerically controlled ultrasonic cleaner (KQ5200DE Kunshan Ultrasonic Instrument Co., Ltd., Kunshan, China), a vortex mixer (CM-1000, EYELA; Tokyo, Japan), and an electronic balance (a PL2002, Mettler Toledo, Zurich, Switzerland).

2.2. Sample Preparation

To fully represent the market, 59 health wine samples were strategically collected from three primary purchase channels: online platforms (22 batches, 37.3%), supermarkets and other retail markets (10 batches, 16.9%), and direct purchase from manufacturers within Hunan Province (27 batches, 45.8%). The distribution of samples by purchase source is presented in Figure 1.
The samples covered a wide range of brands and health-function claims (e.g., antifatigue, kidney-tonifying, and immune regulation). The claimed functions, specifications, purchase sources, and detection results of the individual samples are provided in Table 1. The distribution of samples by claimed function is detailed in Figure 2.

2.3. Standard Solution Preparation

After consulting a review of China’s national food safety surveillance data and relevant literature from 2019 to 2023, 68 PDE-5 inhibitors with high frequencies of illegal adulteration and structural similarities were selected as target analytes.
A mixed stock standard solution of the 68 PDE-5 inhibitors (1000 μg/mL) was prepared in methanol and stored at −20 °C in the dark. To establish the library, the stock solution was diluted to 1000 μg/L with methanol.
The quantitative method was validated on 11 commonly adulterated compounds (e.g., Sildenafil and Tadalafil). For this purpose, individual stock standard solutions (1.0 mg/mL) were first prepared in methanol. A mixed intermediate standard solution (10 μg/mL) was then prepared by combining appropriate volumes of each individual stock solution. Finally, the matrix-matched calibration standard working solutions were prepared at concentrations of 0.8, 1.0, 10, 100, 200, and 400 μg/L by diluting the intermediate solution with the extracted blank health wine matrix obtained from the sample preparation procedure.

2.4. Sample Pretreatment

A 2 mL aliquot of the health wine sample was accurately measured in a 10 mL volumetric flask. After adding 5 mL of acetonitrile, the mixture was sonicated for 30 min and cooled to room temperature. The volume was filled to the 10 mL mark with acetonitrile and mixed thoroughly. The supernatant was passed through a 0.22 μm nylon membrane filter prior to UPLC–Q-TOF/MS analysis.

2.5. UPLC–TOF/MS Conditions

Chromatographic conditions: Separation was performed on an Agilent ZORBAX SB-C18 column (100 mm × 2.1 mm, 1.8 μm) maintained at 30 °C. The mobile phase was (A) 0.1% (v/v) formic acid in water and (B) methanol. The gradient elution program was set as follows: 5% phase B for 0–15 min; 5–98% phase B for 15–17 min; 98–5% phase B for 17–17.5 min; 5% phase B for 17.5–20 min. The flow rate and injection volume were 0.4 mL/min and 5 μL, respectively. The liquid chromatography system was an Agilent 1290 series. It is noteworthy that, to achieve comparable chromatographic separation and performance, the use of a similar UPLC system, column chemistry, and mobile phase is recommended. The mixer volume of the UPLC system was 35 μL.
Mass spectrometric conditions: Analysis was conducted in an Agilent 6545 time-of-flight mass spectrometer (Agilent Technologies, USA) equipped with an electrospray ionization (ESI) source operating in positive ion mode. The data were acquired in the targeted MS/MS mode. Both primary and secondary mass spectra were obtained over a full-scan mass range of m/z = 100–1100. The key source parameters were set as follows: capillary voltage = 3500 V; nozzle voltage = 1000 V; dry gas temperature = 320 °C; dry gas flow rate = 8.0 L/min; nebulizer pressure = 35 psi; sheath gas temperature = 350 °C; sheath gas flow rate = 11 L/min; fragmentor voltage = 120 V.

2.6. Establishment of the High-Resolution Screening Database

The mixed standard working solution (1 μg/mL) was analyzed under the described UPLC–Q-TOF/MS conditions. Data were acquired in both full-scan MS and targeted MS/MS modes at two collision energies (20 and 40 eV). The retention time, accurate precursor mass, and characteristic fragment ions of each compound were extracted from the acquired data using Mass Hunter software (Version 10.1, Agilent Technologies) and imported into Personal Compound Database and Library (PCDL) manager software (Version B.08, Agilent Technologies), building a high-resolution accurate mass spectral library for the 68 target PDE-5 inhibitors.

2.7. Method Validation Procedure

The method for quantifying the 11 selected PDE-5 inhibitors was validated under the Chinese guideline GB/T 27404-2008 [47]. It is important to note that this validation was performed for the analysis of the parent compounds in a food matrix (health wine), not in biological matrices like blood or urine. The validation criteria and requirements for food safety surveillance, which focus on detecting the intact adulterant, are distinct from those required by ICH for pharmacokinetic studies in biological fluids. The validation parameters were linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy (recovery), and precision (relative standard deviation, RSD). The LOD and LOQ were defined as the concentrations yielding signal-to-noise ratios of 3 and 10, respectively. It is crucial to clarify that all LOD and LOQ values reported in this study are expressed in micrograms per liter (μg/L) and represent the sensitivity of the instrumental method, i.e., the concentration in the final solution ready for UPLC-TOF/MS injection. The impact of the sample preparation dilution factor on the overall method sensitivity will be addressed in the Results and Discussion section. The accuracy and precision were evaluated through spike-recovery experiments at the LOQ level in blank health wine matrices. Six replicates were analyzed at this level (n = 6).
For qualitative identification, the criteria established by the World Anti-Doping Agency (WADA) were adopted. A compound was confirmed when the mass accuracy of the precursor ion was within ±5 ppm of the theoretical mass and the retention time matched that of the reference standard within ±0.1 min. For quantitative analysis, the method was validated according to the Chinese guideline GB/T 27404-2008 [47], which aligns with international standards, assessing parameters including linearity, LOD, LOQ, accuracy, and precision.

3. Results

3.1. Establishment and Application of the High-Resolution Screening Database

The retention times, accurate molecular masses, and ionization patterns of the standard solutions of the 68 target PDE-5 inhibitors were analyzed under the optimized chromatographic conditions. The MS/MS spectra were acquired at different collision energies (20 and 40 eV) to generate rich fragmentation information. The data (name, molecular formula, accurate molecular weight, retention time, and corresponding MS/MS spectra at both the collision energies) of each compound were compiled using the Mass Hunter Qualitative (Version B.08, Agilent Technologies) analysis software, establishing a comprehensive, high-resolution accurate mass spectral database for the rapid screening and confirmation of illegally adulterated compounds in suspected samples. The database avoids the need for reference standards and enables the similarity scoring of unknown MS/MS spectra. Table 2 provides detailed information of the 68 compounds, including their molecular formulas and accurate mass-to-charge ratios. The representative MS/MS spectra for all 68 compounds are provided in Figure S1 of the Supplementary Materials.

3.2. Optimization of Instrumental Conditions

Selection of the Chromatographic Column

The separation efficiencies of three Agilent ZORBAX SB-C18 columns (2.1 mm × 150 mm, 5 μm; 2.1 mm × 100 mm, 5 μm; and 2.1 mm × 100 mm, 1.8 μm) for the 11 representative PDE-5 inhibitors in health wine matrices were evaluated via gradient elution with 0.1% (v/v) formic acid in water and methanol. Factors such as the resolution, peak area, and retention time of the three columns were compared. The results indicated that the Agilent ZORBAX SB-C18 column (2.1 mm × 100 mm, 1.8 μm) most effectively separated the 68 analytes, yielding symmetric peak shapes, appropriate retention times, and high response values. Consequently, this column was selected for subsequent analysis.
After optimizing the column, mobile phase composition, and gradient program, the baseline separation of all 68 PDE-5 inhibitors was achieved within 17 min, leading to symmetric peaks and excellent retention time stability (RSD < 0.5%). Under mass spectrometric conditions, the highest ion response for the target analytes was observed at a capillary voltage of 3500 V, nozzle voltage of 1000 V, and sheath gas temperature of 350 °C. The dynamic collision energies (20 and 40 eV) yielded informative fragment ions, notably enhancing the confidence in qualitative identification. The mass accuracy of the precursor ions in the established database was consistently better than 3 ppm, and the matching score for the characteristic fragment ions in the MS/MS spectra exceeded 90%.

3.3. Mass Spectrometric Fragmentation Pathway Analysis of Representative PDE-5 Inhibitors

To demonstrate the reliability of the established spectral library, the fragmentation pathways of three representative PDE-5 inhibitors were investigated in detail. Understanding these characteristic patterns is crucial for reliably identifying known and structurally modified analogs (Figure 3).

3.3.1. Sildenafil (Prototype Drug)

Sildenafil is mainly fragmented around its sulfonylpiperazine moiety. The initial cleavage of the labile N–S bond yields the characteristic fragment ion with m/z = 377. Subsequent breaking of the C–S bond releases a sulfonyl radical (HSO2•), producing the ion with m/z = 311. Further loss of the neutral C2H4 molecule from the ethoxy group on the phenyl ring yields the key fragment ion with m/z = 283. The consistent appearance of this triplet of ions (m/z = 377 > 311 > 283) is a hallmark of the sildenafil core structure. This fragmentation pathway is robust and reproducible, providing a solid foundation for identifying this class of compounds.

3.3.2. Tadalafil (Structural Isomer)

Tadalafil possesses a tryptamine–tryptamine-fused tricyclic scaffold that differs from that of sildenafil, giving rise to a distinct fragmentation pattern. The most abundant fragment ion (m/z = 268) is generated by the loss of the neutral piperonyl ring (C7H6O2, 122 Da). The complementary piperonyl cation appears at m/z = 135. Another characteristic ion (m/z = 262) is formed through a complex Diels–Alder rearrangement reaction involving the loss of methylpiperazinedione. This fragmentation pattern unequivocally differs from that of sildenafil-like compounds and can conclusively identify this structural class.

3.3.3. Vardenafil (N-Ethylpiperazine Variant)

Under our experimental conditions, vardenafil yielded a highly characteristic mass spectrometric fingerprint primarily identifiable by a set of key fragment ions: m/z = 312, m/z = 299, m/z = 284, and m/z = 151. The coexistence of m/z = 312 and m/z = 284 (with a mass difference of 28 Da, corresponding to the loss of C2H4) indicates a sequential dealkylation process involving the ethylpiperazine side chain of vardenafil or a similar structure. Particularly important is the ion at m/z = 151, a diagnostic low-mass fragment likely originating from the ring-opening or rearrangement of a specific cyclic or chain structural unit within the molecule. The m/z = 299 ion is the signature of another parallel fragmentation pathway. The established high-resolution screening method precisely captures and matches all experimentally determined fragment ions of vardenafil with defined mass accuracy, confirming the reliable, high-confidence, and specific identification of vardenafil.
The fragmentation patterns within our database provide a multilayered scientific basis for high-confidence qualitative identification. In particular, they encompass the classic triplet-ion series of sildenafil, the unique rearrangement pathway of tadalafil, and the distinctive mass spectrometric fingerprint of vardenafil constructed from precise experimental data, collectively forming a powerful identification network. This in-depth understanding and utilization of diagnostic fragment ion patterns, particularly the precise matching strategy based on high-resolution mass spectrometric data, substantially enhances the recognition capability and reliability of the method on complex real-world samples, enabling effective differentiation of analogs with subtle structural differences and mitigating the risk of false negatives.

3.4. Method Validation Results

Linearity and Limits of Detection and Quantification: The quantitative method for analyzing the 11 selected PDE-5 inhibitors demonstrated good linearity in the concentration range of 0.8–400 μg/L, with correlation coefficients (r) exceeding 0.9990. The LODs and LOQs, defined as signal-to-noise ratios of 3 and 10, respectively, ranged from 0.2 to 1.0 μg/L and from 0.8 to 4.0 μg/L, respectively. The detailed results are presented in Table 3.
Accuracy and Precision: The accuracy and precision of the method for the 11 PDE-5 inhibitors were assessed through spike-recovery experiments at the LOQ level in blank health wine samples. The average recoveries of the 11 analytes were 71.2–104.1%, with relative standard deviations (RSDs, n = 6) between 3.6% and 10.1% (Table 3). Judging from these results, the method is sufficiently accurate and precise for the quantitative determination of the target compounds.

3.5. Analysis of Real Samples and Discussion

The practical applicability of the established screening database and quantitative method was evaluated using 59 commercial health wine samples. The detection rate was 5.1%, with three batches testing positive for PDE-5 inhibitors. Specifically, one batch was adulterated with sildenafil at a concentration of 0.5 mg/L, and two batches contained tadalafil with concentrations of 1.4 and 32.0 mg/L.

4. Discussion

This study successfully established a high-resolution screening method based on UPLC-TOF/MS and, for the first time, constructed a comprehensive mass spectral database covering 68 PDE-5 inhibitors and their analogs. The primary objective of this work was to address the growing challenge of structural analogs being illegally added to health wines to evade regulatory detection, thereby providing market surveillance authorities with a technical tool for broad-spectrum, efficient, and reliable screening even in the absence of reference standards for all target compounds.
The screening of 59 commercial samples revealed an adulteration rate of 5.1% (3/59). This finding is consistent with trends reported in the recent literature [5,6], indicating that despite intensified regulatory efforts, the illegal addition of PDE-5 inhibitors to health wines marketed for claims such as “anti-fatigue” and “kidney-tonifying” persists, representing an ongoing public health risk. It is particularly noteworthy that two of the three positive samples (S-47 and S-58) were sourced from direct purchase from manufacturers. This is a critical finding, as it strongly suggests that adulteration may be occurring at the production level itself, rather than being limited to post-market tampering in the distribution chain. This insight directs regulatory attention towards the need for enhanced scrutiny and control at the manufacturing source.
Furthermore, the concentration of tadalafil detected in one sample was alarmingly high at 32.0 mg/L. Such a high level poses a significant safety threat to consumers, especially those with underlying cardiovascular conditions. When compared with other studies, the detection of such a high concentration also suggests that illicit manufacturers may be adding excessive amounts in pursuit of rapid “efficacy,” completely disregarding safety boundaries.
The UPLC-TOF/MS method developed in this study effectively overcomes the limitations of traditional methods (e.g., HPLC and targeted LC-MS/MS) outlined in the Introduction. The high resolution, accurate mass measurement, and rapid scanning capabilities of the technique enabled the establishment of a comprehensive spectral library, facilitating non-targeted screening. Unlike methods that predominantly rely on reference standards for targeted analysis, our strategy allows for the identification of unknown or structurally modified analogs, significantly expanding the monitoring scope. Concurrently, the high-throughput nature of the method (analysis of 68 compounds within 17 min) makes it particularly suitable for the large-scale sample screening required for market surveillance. Therefore, this study not only provides a specific detection method but, more importantly, offers a robust solution to combat the evolving strategies of illegal adulteration.
In conclusion, the database and methodology established in this study provide reliable technical support for the screening and regulation of illegally adulterated PDE-5 inhibitors in health wines. Future work will focus on expanding the geographical scope of sample collection and continuously updating the spectral database to include newly emerging analogs, thereby offering more comprehensive technical support for ensuring food safety.

5. Conclusions

This study established an accurate, high-resolution mass spectral database for the rapid screening of 68 PDE-5 inhibitors in health wines. Further, a UPLC–TOF/MS-based method was developed, which enabled the rapid qualitative identification of all target compounds in the absence of reference standards. Our approach achieved broad screening coverage, high sensitivity, and reliable accuracy, enabling effective monitoring of the illegal adulteration of PDE-5 inhibitors and their structural analogs. Risk assessments of commercially available health wines in Hunan Province provided crucial data for market surveillance. In future work, we will expand the sample size across different regions and continuously update the spectral database to include newly emerging analogs, offering more comprehensive technical support for ensuring the safety of health wine products.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/pr13123800/s1. The following Supplementary Materials are included with the submission: Figure S1: Representative MS/MS spectra of the PDE-5 inhibitor standards serving as references for identifying the 68 target compounds.

Author Contributions

Conceptualization, X.H. and B.L.; methodology, X.H. and Z.Y.; validation, X.H. and H.W.; investigation, X.H.; data curation, Y.F.; writing—original draft preparation, X.H. and Y.F.; writing—review and editing, X.H. and Y.D.; project administration, B.L.; funding acquisition, X.H. and L.Y. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Hunan Provincial Natural Science Foundation of China (No. 2022JJ90063).

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, [Xiaobei Huang], upon reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Distribution of sources of the health wine samples.
Figure 1. Distribution of sources of the health wine samples.
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Figure 2. Distribution of the collected health wine samples by claimed function.
Figure 2. Distribution of the collected health wine samples by claimed function.
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Figure 3. Summary of proposed fragmentation pathways generating the common fragments of various PDE-5 analogs.
Figure 3. Summary of proposed fragmentation pathways generating the common fragments of various PDE-5 analogs.
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Table 1. Information summary of the health wine samples analyzed in this study.
Table 1. Information summary of the health wine samples analyzed in this study.
Sample IDClaimed FunctionPurchase SourceSpecificationNoteSample IDClaimed FunctionPurchase SourceSpecificationNote
S-01General HealthRetail Market500 mL, 35% vol.NDS-31Kidney-tonifyingOnline Platform100 mL, 30% vol.ND
S-02Kidney-tonifyingOnline Platform135 mL, 32% vol.NDS-32Kidney-tonifyingOnline Platform500 mL, 35% vol.ND
S-03Kidney-tonifyingOnline Platform125 mL, 35% vol.NDS-33General HealthDirect from Manufacturer500 mL, 35% vol.ND
S-04Kidney-tonifyingRetail Market125 mL, 32% vol.NDS-34General HealthDirect from Manufacturer150 mL, 31% vol.ND
S-05Kidney-tonifyingRetail Market1000 mL, 42% vol.NDS-35General HealthDirect from Manufacturer500 mL, 50% vol.ND
S-06Kidney-tonifyingRetail Market500 mL, 35% vol.NDS-36General HealthDirect from Manufacturer750 mL, 8% vol.ND
S-07Anti-fatigueRetail Market600 mL, 35% vol.NDS-37General HealthDirect from Manufacturer500 mL, 50% vol.ND
S-08Anti-fatigueRetail Market125 mL, 36% vol.NDS-38General HealthDirect from Manufacturer500 mL, 50% vol.ND
S-09Anti-fatigueRetail Market500 mL, 38% vol.NDS-39General HealthDirect from Manufacturer500 mL, 42% vol.ND
S-10General HealthRetail Market500 mL, 38% vol.NDS-40General HealthDirect from Manufacturer500 mL, 52% vol.ND
S-11General HealthRetail Market500 mL, 42% vol.NDS-41Kidney-tonifyingDirect from Manufacturer1000 mL, 42% vol.ND
S-12General HealthRetail Market2500 mL, 38% vol.NDS-42Kidney-tonifyingDirect from Manufacturer500 mL, 35% vol.ND
S-13Kidney-tonifyingOnline Platform500 mL, 35% vol.NDS-43General HealthDirect from Manufacturer500 mL, 52% vol.ND
S-14General HealthOnline Platform110 mL, 33% vol.NDS-44General HealthDirect from Manufacturer100 mL, 42% vol.ND
S-15General HealthOnline Platform110 mL, 33% vol.NDS-45General HealthDirect from Manufacturer500 mL, 52% vol.ND
S-16General HealthOnline Platform500 mL, 38% vol.NDS-46General HealthDirect from Manufacturer500 mL, 52% vol.ND
S-17General HealthOnline Platform75 mL, 35% vol.NDS-47Kidney-tonifyingDirect from Manufacturer500 mL, 53% vol.Positive (Tadalafil)
S-18General HealthOnline Platform500 mL, 35% vol.NDS-48General HealthDirect from Manufacturer500 mL, 52% vol.ND
S-19Kidney-tonifyingOnline Platform500 mL, 35% vol.NDS-49General HealthDirect from Manufacturer500 mL, 52% vol.ND
S-20Kidney-tonifyingOnline Platform125 mL, 38% vol.NDS-50General HealthDirect from Manufacturer500 mL, 45% vol.ND
S-21General HealthOnline Platform125 mL, 38% vol.NDS-51General HealthDirect from Manufacturer275 mL, 3.0% vol.ND
S-22Kidney-tonifyingOnline Platform110 mL, 38% vol.NDS-52General HealthDirect from Manufacturer275 mL, 3.0% vol.ND
S-23Kidney-tonifyingOnline Platform500 mL, 53% vol.Positive (Tadalafil)S-53General HealthDirect from Manufacturer500 mL, 26% vol.ND
S-24Kidney-tonifyingOnline Platform500 mL, 53% vol.NDS-54General HealthDirect from Manufacturer500 mL, 42% vol.ND
S-25Kidney-tonifyingOnline Platform100 mL, 38% vol.NDS-55General HealthDirect from Manufacturer500 mL, 42% vol.ND
S-26General HealthOnline Platform740 mL, 12% vol.NDS-56General HealthDirect from Manufacturer125 mL, 42% vol.ND
S-27General HealthOnline Platform500 mL, 30% vol.NDS-57General HealthDirect from Manufacturer125 mL, 42% vol.ND
S-28General HealthOnline Platform100 mL, 30% vol.NDS-58General HealthDirect from Manufacturer500 mL, 42% vol.Positive (Sildenafil)
S-29Kidney-tonifyingOnline Platform500 mL, 35% vol.NDS-59General HealthDirect from Manufacturer300 mL, 45% vol.ND
S-30Kidney-tonifyingOnline Platform500 mL, 38% vol.ND
Note: ND, not detected (below the detection limit).
Table 2. Information of the reference standards, precursor ions, retention time, major product ions, number of MS/MS spectra and ionization mode of the 68 compounds.
Table 2. Information of the reference standards, precursor ions, retention time, major product ions, number of MS/MS spectra and ionization mode of the 68 compounds.
No.Compound NameMolecular FormulaPrecursor Ions
(m/z)		Mass Error (ppm)Retention Time
(min)		Major Product Ions (m/z)CAS No.Number of MS/MS SpectraIonization Mode
1SildenafilC22H30N6O4S475.21221.55.681377.1272, 283.1191, 151.0862, 100.0996139755-83-22ESI+
2TadalafilC22H19N3O4390.1448−0.87.097268.1082, 262.0860, 240.1126, 169.0755, 151.0754, 135.0437171596-29-52ESI+
3ImidazosagatriazinoneC17H20N4O2313.16592.19.734285.1349, 256.0956, 241.0726, 201.0537, 166.0974, 136.0506, 120.0448139756-21-12ESI+
4GendenafilC19H22N4O3355.1765−1.28.334327.1455, 311.1141, 298.1061, 285.1347, 256.0958, 216.0765, 166.0973147676-66-22ESI+
5Acetil acidC18H20N4O4357.15570.57.075329.1246, 300.0851, 285.1345, 268.1083, 256.0955, 166.0973147676-78-62ESI+
6XanthoanthrafilC19H23N3O6390.166−2.37.263151.0755, 135.0437, 107.04911020251-53-92ESI+
7AminotadalafilC21H18N4O4391.140136.433269.1036, 262.0862, 233.0829, 205.0880, 169.0759, 135.0439385769-84-62ESI+
8ChloropretadalafilC22H19ClN2O5427.1055−1.79.243334.1077, 302.0811, 274.0864, 262.0864, 135.0440171489-59-12ESI+
9PiperiacetildenafilC24H31N5O3438.250.95.576341.1610, 325.1299, 313.1300, 297.1347, 166.0974147676-50-41ESI+
10CarbodenafilC24H32N6O3453.2609−2.84.802339.1452, 311.1141, 166.0973, 147.0076, 113.1076944241-52-51ESI+
11PseudovardenafilC22H29N5O4S460.20131.18.332312.1584, 301.1297, 299.1144, 284.1270, 151.0866224788-34-52ESI+
12NorneosildenafilC22H29N5O4S460.2013−0.410.199432.1698, 329.1607, 312.1580, 299.1143, 283.1191, 256.0959371959-09-02ESI+
13N-DesmethylsildenafilC21H28N6O4S461.19662.54.725377.1280, 361.1328, 311.1507, 299.1142, 283.1192139755-82-11ESI+
14AcetildenafilC25H34N6O3467.2765−1.95.162341.1610, 325.1657, 297.1347, 127.1230, 111.0916831217-01-72ESI+
15AvanafilC23H26ClN7O3484.18580.75.633375.1221, 357.1115, 233.1033, 155.0257330784-47-92ESI+
16VardenafilC23H32N6O4S489.2279−2.14.853376.1058, 312.1579, 285.1314, 198.0538, 151.0855, 133.1069224785-90-42ESI+
17ThiosildenafilC22H30N6O3S2491.18941.87.557341.1428, 327.1272, 313.1112, 299.0962, 100.0995479073-79-52ESI+
18HydroxyhomosildenafilC23H32N6O5S505.2228−0.65.593487.2119, 377.1277, 311.1505, 283.1191, 129.1020, 112.0995, 100.0977139755-85-42ESI+
19UdenafilC25H36N6O4S517.25922.86.201474.2170, 325.1664, 299.1141, 283.1193, 191.0848, 112.1120268203-93-61ESI+
20HydroxythiohomosildenafilC23H32N6O4S2521.1999−1.47.407503.1891, 327.1274, 315.0909, 299.0964, 129.1020, 112.0995479073-82-02ESI+
21NorneovardenafilC18H20N4O4357.15570.35.416329.1237, 300.0854, 151.0865, 123.0919358390-39-32ESI+
22NitrodenafilC17H19N5O4358.151−2.99.331330.1199, 312.1582, 284.1269, 256.0956, 136.0506147676-99-12ESI+
23NortadalafilC21H17N3O4376.12921.66.561302.0812, 274.0859, 263.0935, 262.0861, 254.0925, 169.0758, 135.0438171596-36-42ESI+
24HydroxychlorodenafilC19H23ClN4O3391.1531−0.98.114363.1220, 313.1297, 285.1348, 256.0957, 166.09741391054-00-42ESI+
25N-ButyltadalafilC25H25N3O4432.19182.28.938310.1553, 282.1601, 262.0861, 169.0762, 135.0440171596-31-92ESI+
26DesmethylcarbodenafilC23H30N6O3439.2452−1.14.675339.1454, 311.1141, 297.1345, 283.1188, 166.0974147676-79-72ESI+
27DescarbonsildenafilC21H30N6O4S463.21220.45.244418.1544, 311.1505, 297.1343, 283.1192, 127.1229, 111.09141393816-99-32ESI+
28OxohongdenafilC25H32N6O4481.2558−3.15.738410.2191, 396.2030, 375.1223, 325.1298, 297.1348, 155.02591446144-70-22ESI+
29N-OctylnortadalafilC29H33N3O4488.25441.311.544366.2177, 302.0812, 262.0862, 197.0708, 169.0759, 135.04401173706-35-82ESI+
30DioxohongdenafilC25H30N6O5495.235−26.695369.1383, 341.1070, 311.1139, 127.08651609405-33-52ESI+
31HydroxythiovardenafilC23H32N6O4S2521.19992.76.212393.1041, 328.1351, 315.0909, 299.0961, 167.0638912576-30-81ESI+
32CyclopentynafilC26H36N6O4S529.2592−0.55.338461.1966, 377.1268, 312.1581, 284.1263, 151.0866, 112.11181173706-34-72ESI+
33Propoxyphenyl thiohydroxyhomosildenafilC24H34N6O4S2535.21561.97.982341.1430, 315.0911, 299.0964, 271.1010, 129.1020, 100.0979479073-90-02ESI+
34BenzylsildenafilC28H34N6O4S551.2435−1.87.053459.1804, 377.1278, 355.1763, 312.1579, 134.0963, 117.06991446089-82-22ESI+
35CinnamyldenafilC32H38N6O3555.30780.27.23437.2299, 355.1767, 339.1455, 117.06961446089-83-32ESI+
36Lodenafil carbonateC47H62N12O11S21035.4175−2.58.9519.2206, 487.2120398507-55-61ESI+
37AcetaminotadalafilC23H20N4O5433.15061.46.367383.1717, 371.1717, 355.1395, 312.1580, 262.0861, 169.0758, 135.04391446144-71-32ESI+
382-HydroxypropylnortadalafilC24H23N3O5434.171−0.76.804312.1347, 284.1393, 262.0861, 197.0706, 169.0758, 135.04381353020-85-52ESI+
39AcetylvardenafilC25H34N6O3467.27652.94.105396.2029, 355.1758, 341.1608, 297.1345, 151.0863, 127.1228, 111.09161261351-28-32ESI+
40PropoxyphenylhydroxyhomosildenafilC24H34N6O5S519.2384−1.36.085501.2274, 328.1351, 299.1071, 283.1190, 167.0639, 129.1020139755-87-62ESI+
41YohimbineC21H26N2O3355.20160.84.315224.1280, 212.1281, 194.1176, 144.0807146-48-52ESI+
42DapoxetineC21H23NO306.1852−2.27.086261.1277, 233.0962, 183.0804, 157.0648, 117.0697119356-77-32ESI+
43DesmethylthiosildenafilC21H28N6O3S2477.17371.77.436393.1048, 327.1273, 315.0911, 299.0963, 271.1009479073-86-42ESI+
44N-Boc-N-desethyl acetildenafilC28H38N6O5539.2976−0.96.898439.2455, 353.1609, 339.1816, 297.1346, 100.09481246820-46-12ESI+
45N-EthyltadalafilC23H21N3O4404.16052.47.622364.1072, 282.1238, 262.0862, 169.0759, 135.04381609405-34-62ESI+
46O-DesethylsildenafilC20H26N6O4S447.1809−1.65.869415.1980, 371.1715, 347.0811, 283.1192, 101.1076139755-91-22ESI+
47Vardenafil oxopiperazineC21H26N6O5S475.17580.55.453312.1578, 299.1137, 283.1190, 151.0864, 100.0997448184-58-52ESI+
48Vardenafil N-oxideC23H32N6O5S505.2228−2.74.974477.1910, 377.1275, 335.1112, 312.1583, 151.0862, 113.1074448184-48-32ESI+
492-HydroxyethylnortadalafilC23H21N3O5420.15541.16.439302.0808, 274.0863, 262.0863, 197.0707, 169.0758, 135.0440385769-94-81ESI+
50Vardenafil acetyl analogueC24H31N5O3438.25−0.34.409341.1610, 325.1299, 311.1144, 297.1347, 151.0866224785-90-42ESI+
51Vardenafil dimerC38H46N10O8S2835.301428.618312.1581, 151.08621255919-03-91ESI+
52MirodenafilC26H37N5O5S532.2588−1.87.025514.2480, 404.1634, 339.1876, 312.1343, 296.1395, 129.1019862189-95-52ESI+
53MutaprodenafilC27H35N9O5S2630.22750.67.191525.2225, 488.2167, 377.1279, 312.1560, 142.0068, 113.10721387577-30-12ESI+
54ThioquinapiperfilC24H28N6OS449.2118−2.44.586339.1450, 311.1142, 204.1382, 186.1280220060-39-92ESI+
55AminosildenafilC18H23N5O4S406.15441.87.219364.1073, 299.1141, 283.1191, 255.1243, 166.0974319491-68-42ESI+
56DesethylcarbodenafilC22H28N6O3425.2296−0.54.559339.1453, 311.1140, 166.0975, 147.00761027192-92-22ESI+
57DidescarbonsildenafilC20H28N6O4S449.19662.35.117312.1566, 311.1505, 283.1191, 204.1380, 166.0974, 121.0647466684-88-82ESI+
58N-PhenylpropenyltadalafilC30H24N4O4505.187−1.99.664383.1502, 299.0960, 262.0863, 169.0755, 135.0438, 113.10712064212-00-42ESI+
59N-Desethyl-N-methylvardenafilC22H30N6O4S475.21220.74.754376.1074, 312.1584, 299.1140, 151.0866224785-87-92ESI+
60DichlorodenafilC19H20Cl2N4O2407.10362.512.057379.0726, 363.0415, 350.0336, 343.0957, 280.0953, 166.0973, 136.05051446089-84-42ESI+
61Propoxyphenyl thiosildenafilC23H32N6O3S2505.205−0.88.175355.1590, 313.1118, 299.0964, 271.1012, 113.1074479073-87-52ESI+
62Dithiodesethyl carbodenafilC22H28N6OS2457.18391.47.55371.0997, 343.0685, 309.0802, 178.96201610830-81-32ESI+
63HydroxythioacetildenafilC25H34N6O3S499.2486−2.16.794369.1385, 341.1069, 313.1127, 143.1178, 127.08641159977-47-52ESI+
64Tadalafil dichloro impurityC22H18Cl2N2O5461.06660.910.078312.1559, 300.1173, 284.1236, 274.0862, 262.0860, 135.04381598416-08-02ESI+
65Sildenafil impurity 4C25H34N6OS2499.2308−1.28.177468.1886, 428.1575, 371.1000, 343.0687, 178.96222520113-03-32ESI+
66Demethylpiperaziny sildenafil sulfonic acidC17H20N4O5S393.12272.84.586365.0913, 336.0524, 285.1334, 256.0955, 136.05051357931-55-52ESI+
67Propoxyphenyl aildenafilC24H34N6O4S503.2435−0.46.494391.1432, 325.1660, 299.1143, 283.1190, 113.10741391053-82-91ESI+
68Sildenafil impurity 14C24H32N6OS2485.21521.68.016468.1881, 428.1573, 371.0999, 343.06822146091-79-22ESI+
Table 3. Linear ranges, correlation coefficients (r), LODs, LOQs, recoveries, and RSDs (n = 6) of the 11 PDE-5 inhibitors.
Table 3. Linear ranges, correlation coefficients (r), LODs, LOQs, recoveries, and RSDs (n = 6) of the 11 PDE-5 inhibitors.
NO.CompoundLinear Range (μg/L)rLOD (μg/L)LOQ (μg/L)Recovery (%)RSD (%)
1Nor-acetildenafil2.0–2000.99980.52.083.56.5
2Acetildenafil4.0–4000.99961.04.081.410.1
3Vardenafil4.0–4000.99911.04.089.03.9
4Hydroxyhomosildenafil0.8–800.99900.20.886.54.2
5Sildenafil2.0–2000.99980.52.087.65.8
6Homosildenafil2.0–2000.99970.52.071.26.8
7AminoTadalafil2.0–2000.99930.52.0104.18.0
8Tadalafil4.0–4000.99981.04.089.97.1
9Thioaildenafil4.0–4000.99961.04.085.84.3
10PseudoVardenafil0.8–800.99910.20.896.06.4
11NorneoSildenafil2.0–2000.99880.52.073.13.6
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MDPI and ACS Style

Huang, X.; Li, B.; Wang, H.; Yang, L.; Yi, Z.; Fu, Y.; Du, Y. Rapid Screening and Identification of Illegally Adulterated PDE-5 Inhibitors in Health Wines by UPLC-TOF-MS. Processes 2025, 13, 3800. https://doi.org/10.3390/pr13123800

AMA Style

Huang X, Li B, Wang H, Yang L, Yi Z, Fu Y, Du Y. Rapid Screening and Identification of Illegally Adulterated PDE-5 Inhibitors in Health Wines by UPLC-TOF-MS. Processes. 2025; 13(12):3800. https://doi.org/10.3390/pr13123800

Chicago/Turabian Style

Huang, Xiaobei, Ben Li, Hui Wang, Lixia Yang, Zi Yi, Yuli Fu, and Yun Du. 2025. "Rapid Screening and Identification of Illegally Adulterated PDE-5 Inhibitors in Health Wines by UPLC-TOF-MS" Processes 13, no. 12: 3800. https://doi.org/10.3390/pr13123800

APA Style

Huang, X., Li, B., Wang, H., Yang, L., Yi, Z., Fu, Y., & Du, Y. (2025). Rapid Screening and Identification of Illegally Adulterated PDE-5 Inhibitors in Health Wines by UPLC-TOF-MS. Processes, 13(12), 3800. https://doi.org/10.3390/pr13123800

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