Degradation Pathways and Energy Efficiency on Non-Thermal Plasma for Sulfonamide Antibiotics Removal: A Comparative Study

Abstract

The non-thermal plasma (NTP) process is a promising advanced oxidation process (AOP) for removing non-biodegradable organics from wastewater, owing to the efficient formation of reactive chemicals. Despite its effective oxidizing capability, the decomposition mechanism of organic pollutants is not well understood. This study evaluates NTP for two representative sulfonamides (SMZ and STZ) and reports on (i) time-resolved removal to the method detection limit, (ii) transformation mapping using LC-ESI/MS/MS, which confirmed previously proposed hydroxylation and bond-cleavage pathways and further identified additional hydroxylated intermediates formed on the thiazole and benzene rings under NTP conditions, and (iii) energy evaluation through energy per order (EEO) within a single, reproducible operating window. The EEO values for SMZ and STZ degradation via NTP were calculated at 22.4 and 7.5 kWh/m³/order, respectively. These values are up to 37- and 118-fold lower than those reported for comparable AOPs, quantitatively confirming that the proposed NTP process achieves superior energy efficiency for sulfonamide degradation. Degradation is primarily attributed to reactive oxygen species (ROS) generated by plasma, which initiate the breakdown of the antibiotic structure. Overall, this study demonstrates that NTP is a highly effective AOP for driving the rapid primary degradation and intermediate structural transformation of recalcitrant sulfonamide antibiotics.

1. Introduction

Antibiotics are commonly used to protect human and animal health by treating pathogenic infections. They are used worldwide, totaling approximately 200,000 tons annually, and have numerous benefits [1]. Antibiotics are frequently introduced into both soil and water systems due to their continued use [2]. These residual antibiotics enter the environment through industrial spills, municipal wastewater, animal breeding, and aquaculture, posing new threats to ecosystems and humans, including the emergence of super bacteria in water systems [1,3,4,5]. These residual antibiotics are considered contaminants of emerging concern (CEC) [6]. Furthermore, antibiotics are challenging to remove using traditional biological methods in wastewater treatment plants because of their antibacterial properties [3], and they are highly susceptible to exposure in aquatic systems.

Although there are various types of antibiotics, sulfonamide group antibiotics are synthesized from sulfanilamide and are widely used to treat diseases caused by bacteria and other microorganisms in humans, livestock, and fish [7]. Sulfonamide antibiotics are now ubiquitous in aquatic environments, ranging from ng/L in surface waters to tens or hundreds of µg/L in livestock wastewater and streams near concentrated animal feedlots [2,8]. However, residual sulfonamide group antibiotics in water systems are classified as CEC because of their pathogenicity and carcinogenicity [9]. Unfortunately, sulfonamide group antibiotics are non-biodegradable pollutants, making them challenging to remove using traditional treatment methods [10]. Therefore, advanced processes are required for effective antibiotic treatment.

Research is ongoing into physicochemical treatments to eliminate both degradable and non-degradable pollutants, including pathogens, eco-toxins, and antibiotics, to overcome the limitations of conventional biological water treatment processes [11,12,13]. Additionally, it is difficult to expect continuous removal efficiency with biological treatment because of the accumulation of antibiotics [14]. Among the tested approaches, advanced oxidation processes (AOP), known for their capability to remove high concentrations of organic materials and non-biodegradable pollutants, show particular promise [15,16,17].

The non-thermal plasma (NTP) has garnered attention as a promising AOP due to its unique ability to ionize a carrier gas, leading to the physicochemical formation of reactive species, including photons, electrons, radicals, electromagnetic energy, charged particles, and more [12,18,19]. The NTP process generates potent oxidizing agents that play a significant role in removing non-biodegradable organic pollutants from wastewater [12,20]. The reactive chemicals generated by NTP are sufficiently effective in non-selectively reacting with target pollutants [21]. Furthermore, NTP technology eliminates the need for chemical injections and can reduce secondary contamination [22,23]. Additionally, NTP is less affected by conditions such as pH, temperature, and turbidity than other AOPs [24]. It should be noted that the degradation performance and energy consumption of NTP can vary depending on the discharge type, including glow discharge, corona discharge, dielectric barrier discharge (DBD), and sliding arc discharge, each of which differs in reactive species generation and mass transfer characteristics [25]. However, there is insufficient research on the mechanisms or degradation pathways that explain the reduction in antibiotics, the decomposition of pollutants, and energy efficiency in the context of NTP.

Therefore, this study aimed to investigate (i) the degradation kinetics of sulfamethazine (SMZ) and sulfathiazole (STZ) under the applied NTP operating conditions, (ii) the dominant degradation pathways, elucidated through the identification of transformation products by liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI/MS/MS), and (iii) the comparative energy efficiency, evaluated using the energy per order (EEO) metric. This study is anticipated to provide critical data on the decomposition mechanisms of sulfonamides and a clear basis for evaluating the advantages of the NTP process over alternative methods.

2. Materials and Methods

2.1. Experimental Set-Up of the NTP

In this study, a glow-discharge-based NTP reactor (Groon Co., Ltd., Jeonju, Republic of Korea) with a pin-to-plate electrode structure was employed. The system was operated at a continuous plasma power input of 18.4 W. This specific reactor configuration has been previously validated by our research group for highly efficient treatment of diverse contaminants, including parabens [26] and perfluorooctanesulfonic acid (PFOS) [27]. Degradation experiments were conducted in a batch configuration with a 1 L working volume. Atmospheric air, serving as the feed gas for ROS generation, was continuously injected into the aqueous phase at a controlled flow rate of 5 L/min via an air pump (19 W; Shinhwa Hightech, Gwangju-si, Republic of Korea, ZP-25) equipped with a submerged ceramic diffuser connected downstream of the NTP unit. A closed space in which plasma was generated was used to blow atmospheric air into the reaction tank, where it directly contacted the chemicals in water. The plasma generator power was set to 18.4 W, and the airflow rate injected into the reactor through the aeration pump was fixed at 5 L/min for each reactor using a flow meter (Dwyer Instruments, Inc., Michigan City, IN, USA, Model No. RMA-22-SSV). A flow rate of 5 L/min was selected as the optimal value based on previous reports [15]. The air inlet hoses had inner diameters of 6 and 8 mm. The experimental setup closely followed that of a previous study [19]. The reactor was operated with a sealed lid to minimize evaporative losses, and the sampling volume was restricted to 0.5 mL per event to further limit volume reduction during operation. No visually appreciable change in reactor volume was observed throughout the experimental period.

2.2. Chemical Characteristics

To evaluate the degradation efficiency of antibiotics, this study tested two sulfonamide sodium salt group antibiotics. SMZ and STZ were selected as structurally representative, widely detected sulfonamides that share a common benzene-sulfonamide core but differ in their heterocyclic substituents (a pyrimidine ring in SMZ and a thiazole ring in STZ). Crucially, this structural divergence inherently influences their susceptibility to ROS-mediated oxidation. The thiazole ring in STZ possesses elevated electron density at the sulfur atom, rendering it highly susceptible to electrophilic attack by ⋅OH [28]. Conversely, the electron-withdrawing nature of the diazine structure in SMZ’s pyrimidine ring makes it comparatively less reactive. Consequently, this pair serves as an ideal structural model to investigate how specific heterocyclic moieties govern degradation efficiency under NTP conditions. SMZ and STZ were selected as structurally representative, widely detected sulfonamides that share a common benzene-sulfonamide core but differ in their heterocyclic substituents (a pyrimidine ring in SMZ and a thiazole ring in STZ). Crucially, this structural divergence inherently influences their susceptibility to ROS-mediated oxidation. The thiazole ring in STZ possesses elevated electron density at the sulfur atom, rendering it highly susceptible to electrophilic attack by ⋅OH [26]. Conversely, the electron-withdrawing nature of the diazine structure in SMZ’s pyrimidine ring makes it comparatively less reactive. Consequently, this pair serves as an ideal structural model to investigate how specific heterocyclic moieties govern degradation efficiency under NTP conditions. To facilitate dissolution in dilution water, sodium salts of the antibiotics were used. The antibiotics were purchased from Sigma-Aldrich (Steinheim, Germany).

2.3. Analytical Procedures

To verify the transformation and degradation pathways of the antibiotics, by-products were first identified using high-performance liquid chromatography (HPLC) (2690XE, Waters Corp., Milford, MA, USA), and the final by-products and overall pathways were identified using hybrid tandem LC-MS/MS (Synapt G2-Si HDMS, Waters, Milford, MA, USA). The MS/MS spectra of the by-products were compared with those of the initial antibiotics to determine whether the chemical had changed by NTP. These analytical results indicate the degradation of the parent compounds and the subsequent formation of tentatively identified intermediate transformation products.

An LC-ESI/MS/MS Triple Quadrupole (6410 LC-MS/MS, Agilent, Santa Clara, CA, USA) was equipped with HPLC and an electrospray ionization source (Agilent Technologies, Santa Clara, CA, USA) was used. Chromatographic separation was performed using a Shim-pack VP-ODS C18 (150 mm × 4.6 mm, 5 m) column. All data analyzed were collected using Agilent 6410 Quantitative Analysis data processing software (Agilent Technologies, Santa Clara, CA, USA). The mobile phase, a mixture of methanol 5 mM and ammonium acetate solution (80:20, v/v), was injected at a flow rate of 0.4 mL/min. The column oven temperature was 30 °C, and the sample injection volume was 10.0 μL. Mass spectrometric detection was performed using a Series 6410 Triple Quad LC-MS/MS (Agilent Technologies, Santa Clara, CA, USA) with multiple reaction monitoring.

Mass spectrometric detection was performed using positive electrospray ionization (ESI+) mode. For targeted quantification, multiple reaction monitoring (MRM) transitions were optimized using the Agilent MassHunter Optimizer software (Agilent Technologies, Santa Clara, CA, USA). Quantification was performed using the [M + H]⁺ precursor ions at m/z 279 for SMZ and m/z 256 for STZ, with their most abundant product ions at m/z 186 and m/z 156, respectively, corresponding to the characteristic cleavage of the sulfonamide S-N bond [29,30].

External calibration standards of 1, 10, 100, and 1000 μg/L were used for LC-MS/MS quantification. In this study, 1 μg/L (equal to 1000 ng/L), the lowest calibration level, was used as the practical reporting threshold, and concentrations below this level were treated as non-detect (N.D.). Identification of unknown transformation products was conducted using LC-MS/MS-derived exact masses, observed m/z values, retention times, isotope patterns, and matching MS/MS fragment ions via the UNIFI workflow database.

Because authentic reference standards were not used for final confirmation, all reported intermediate by-products are considered tentative identifications. To provide transparent analytical rationales for these structural assignments, the detailed mass spectrometric parameters, including observed retention times, precursor exact masses, and key diagnostic MS/MS fragment ions used for structural elucidation, are comprehensively cataloged in Table S1 (for SMZ) and Table S2 (for STZ) of the Supplementary Information.

2.4. Calculation of Energy per Order

Energy per order (EEO) is widely used to assess and compare the electrical costs of various AOPs [31]. We calculated the EEO for each treatment using Equation (1), as in a previous study [20].

$$\mathrm{EEO}={\displaystyle \frac{P·t·1000}{V·60·\mathrm{l}\mathrm{o}\mathrm{g}\left(\frac{Co}{Ct}\right)}}$$

(1)

where P is the power of the equipment (kW), t is the reaction time (min), V is the volume of water (L), C₀ is the initial concentration, and C_t is the concentration at time t (min). The power parameter (p, in kW) represents the total system electrical input power, empirically determined by recording cumulative active energy consumption (kWh) via an inline power monitoring device and dividing it by the treatment time. Because the air pump is physically integrated into the NTP unit and draws power from a single shared electrical connection, the measured P value inherently accounts for the power demands of both the plasma generator and all auxiliary equipment. Consequently, the reported EEO metrics account for total systemic energy requirements, providing a realistic, conservative assessment of the system’s overall efficiency.

2.5. Statistical Analysis

The removal rate constant, k (h⁻¹), was determined using the SigmaPlot software (version 14, Systat Software, Inc., San Jose, CA, USA) by performing regression analysis based on the assumptions of first-order exponential decay. We calculated using the following Equation (2):

[C_t] = [C_o]e^−kt

(2)

where [C_o] represents the initial concentration, [C_t] represents the concentration of the sample at reaction time t (h), and k is the pseudo-first-order rate constant.

3. Results and Discussion

3.1. Parent Antibiotics Degradation from NTP Treatment

Figure 1 illustrates the degradation patterns of antibiotics in distilled water. Initial concentrations of 320 µg/L (SMZ) and 600 µg/L (STZ) were selected to simulate ‘worst-case’ environmental contamination scenarios while simultaneously ensuring robust LC-MS/MS quantification and kinetic modeling. These sub-mg/L levels are consistent with concentrations reported in highly impacted aquatic systems; for instance, SMZ has been detected at up to 21.3 µg/L in streams receiving agricultural runoff in Korea, and other sulfonamides have been reported at concentrations exceeding 100 µg/L in untreated wastewater effluents [8]. An initial induction period was observed before rapid degradation (about 1 h for SMZ and 2 h for STZ). This lag phase is a characteristic interfacial phenomenon in gas–liquid NTP systems, reflecting the finite mass-transfer time required for gas-phase ROS to solubilize and reach steady-state concentrations in the bulk aqueous phase. Furthermore, the extended induction period for STZ is consistent with its higher initial loading concentration (600 µg/L compared to 320 µg/L for SMZ), which inherently exerts a greater initial stoichiometric demand for ROS before significant parent-compound depletion can be analytically detected.

The initial concentration of SMZ sodium salt was approximately 320 μg/L. The SMZ sodium salt showed resistance to oxidation for approximately 1 h, but by the 2-hour mark, the degradation efficiency reached 10.4%. After 18 h, the degradation efficiency increased to 71.3%, and by 48 h, the concentration dropped below the detection limit.

For STZ sodium salt with an initial concentration of approximately 600 μg/L, the parent antibiotics were resistant to oxidation, showing no significant change for approximately 2 h. However, after 6 h, the degradation efficiency reached 10.5%, and the removal efficiency continued to increase over time. After 24 h, the initial concentration decreased to less than half its original value, yielding a degradation efficiency of approximately 56.7%. The concentration fell below the detection limit at 144 h.

The results obtained using the NTP process experimentally demonstrated its feasibility as an extension of several AOPs. As with other types of AOPs, the NTP process generates reactive oxygen species (ROS) [32], which are believed to oxidatively decompose the sodium salts of SMZ and STZ. Zhou et al. [33] reported that specific sites in the oxidation reactions of the aniline and isoxazole rings of sulfamethoxazole were affected, observing ozone (O₃)-mediated oxidation and hydroxylation in both the aniline and isoxazole moieties. When these antibiotics came into contact with the generated radical species, the N-H bond was the most actively decomposed [34]. Detailed results regarding the degradation pathways are provided in Section 3.3.

3.2. Degradation Efficiency and Kinetics of NTP Versus Other Processes

Table 1. Contextual comparison of pseudo-first-order rate constants and removal efficiencies for SMZ and STZ degradation across various advanced oxidation processes.

Item	Process	Removal Efficiency (%)	k (h−1)	95% CI (h−1)	R2
SMZ	NTP (This study)	99.9	0.0731	[0.0596–0.0866]	0.99
	O3/H2O2 [7]	86.3	1.74		0.97
	TAP (Thermally activated persulfate) [35]	11~100	0.318~84.018		0.7636~0.9968
	Cu/PMS [36]	82.6	-		-
	US-PS [37]	24.4	-		-
	nZVC-PS [37]	56.6	-		-
	nZVC-PS-US [37]	96.4	-		-
	Cu2+ activated persulfate [38]	96.5	-		-
STZ	NTP (This study)	99.9	0.0276	[0.0238–0.0314]	0.98
	O3/H2O2 [7]	89.3	1.74		0.97
	UV/Na2S2O8 [39]	96	0.846		0.97
	UV/NaBrO3 [39]	99	1.368		0.99
	UV/TiO2 [40]	99.9	1.14		0.98
	4-CQDs/BiOCOOH/uCN 50 [41]	99.2	-		-

summarizes representative AOPs for SMZ and STZ degradation to provide a broader context for the present NTP results. Under the applied operating conditions, the NTP process achieved 99.9% removal of both SMZ and STZ, yielding apparent pseudo-first-order rate constants k_obs of 0.0731 h⁻¹ (95% CI: 0.0596–0.0866) and 0.0276 h⁻¹ (95% CI: 0.0238–0.0314), respectively. While several studies report higher apparent rate constants or shorter treatment times [7,35,36,37,38], these external values were obtained under highly heterogeneous experimental conditions, including substantial variations in initial pollutant concentrations, catalyst loadings, external oxidant dosages, UV irradiation intensities, and optimized pH windows. Consequently, direct cross-study comparisons of these kinetic constants are inherently limited and must be interpreted with caution.

Table 1 is therefore presented strictly as a qualitative, contextual benchmark rather than a definitive ranking of intrinsic catalytic performance. Many comparable systems achieve rapid degradation kinetics only by relying on the continuous, costly dosing of external oxidants or sacrificial catalysts [35,36,37,38,39,40,41]. By contrast, the principal engineering advantage of the proposed NTP system is not necessarily achieving the highest absolute kinetic rate, but rather its remarkable operational simplicity: it achieves near-complete degradation of sub-mg/L sulfonamides utilizing only ambient air, entirely devoid of chemical additives.

Because of this extreme heterogeneity in chemical inputs across different AOPs, energy-based evaluations (EEO) provide a far more standardized and meaningful metric for practical, real-world comparative analysis than apparent k-values alone.

3.3. Degradation Pathways on Chemical Transformation of Target Antibiotics

Figure 2 illustrates that sulfonamide sodium salt antibiotics share a basic structure with different substituents on sulfanilamide. The [M + H]⁺ ions of STZ sodium salt and SMZ sodium salt antibiotics have m/z values of 256 and 279, respectively. The daughter ions obtained by the fragmentation of [M + H]⁺ ions had m/z values of 92 and 108 [42], respectively. Two water-soluble antibiotics were employed to determine the chemical changes and pathways of the tested compounds. The peak values of the antibiotic at its initial concentration and its concentration before complete removal were compared to determine the degradation pathways. The m/z values were used to identify intermediates and by-products. Figure 3 illustrates the changes in the LC-MS chromatograms over various treatment times for the two water-soluble antibiotics.

The background peak was measured using the initial methanol and compared with the peak of antibiotics pre-treated with methanol to identify the intermediate by-product. The presence of both types of antibiotics gradually decreased as exposure to NTP increased, and neither was detected after 3 days. The predicted peaks of the by-products generated during decomposition initially appeared and then diminished as the treatment time increased. The peak intensity also initially increased and then decreased.

It is presumed that the initial antibiotic is converted into an intermediate degradation product by NTP treatment and then further transformed into a final degradation product, such as an organic acid or an inorganic substance [43]. The SMZ sodium salt showed more peaks than the STZ sodium salt, suggesting that a wider range of decomposition products was produced (Figure 3). As decomposition progressed, most peaks decreased gradually.

Table 2. Tentatively identified intermediate and transformation by-products of the SMZ sodium salt based on exact mass and LC-MS/MS fragmentation profiles.

Component Name	Neutral Mass (Da)	Observed Neutral Mass (Da)	Observed m/z	Observed RT (min)	Isotope Match Mz RMS PPM
3-(1-Methyl-1H-pyrrol-2-yl)-1H-pyrazole-5-carboxylic acid	191.07	191.07	192.07	1.47	2.69
5-Amino-2-(3,5-dimethyl-1H-pyrazol-1-yl)benzoic acid	231.10	231.10	232.11	2.30	2.26
Methyl-4-([4-(carbamimidoylsulfamoyl)pheny]amino-4-oxobutanoate	328.08	328.08	329.09	2.83	1.65
2-(2-Isopropyl-5-methylphenoxy)-N-(4-sulfamoylphenyl)acetamide	362.13	362.13	363.14	2.81	13.14
N-[(E)-(2-[(4-Aminophenyl) sulfonyl] hydrazine) methylene]acetamide	256.06	256.06	257.07	2.95	2.67
Sulfacytine	294.08	294.08	295.09	3.46	1.31
4-[(4,6-Dimethyl-2-pyrimidinyl)amino]benzenesulfonamide	278.08	278.08	279.09	3.56	2.39
N-[4-(2-Pyrimidinylsulfamoyl)phenyl]propanamide	306.08	306.08	307.09	3.68	2.57

presents the tentatively identified decomposition products from LC-MS/MS analysis, including exact masses and fragmentation patterns.

The degradation pathway of SMZ sodium salt through NTP treatment is illustrated in Figure 4. The decomposition of SMZ sodium salt is initiated by ROS radical reactions within the antibiotic structure, resulting in the formation of hydroxyl groups as ROS radicals replace the amino groups. Intermediate by-products formed through the dissociation of the S-N bond in the compound were also identified.

Table 3. Tentatively identified intermediate and transformation by-products of the STZ sodium salt based on exact mass and LC-MS/MS fragmentation profiles.

Component Name	Neutral Mass (Da)	Observed Neutral Mass (Da)	Observed m/z	Observed RT (min)	Isotope Match Mz RMS PPM
2-[(2,2-Dimethylpropyl)sulfonyl] ethyl dihydrogen phosphate	260.05	260.05	261.06	0.58	0.53
Sulfanilic acid	173.01	173.01	174.02	1.18	1.66
4-(1,3-Thiazol-2-ylsulfamoyl)-1H-pyrrole-2-carboxylic acid	272.99	272.99	273.99	1.28	3.44
N-[(4-Sulfamoylphenyl)carbamothioyl]glycine	289.02	289.02	290.03	1.85	1.04
Methyl-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]carbamate	313.02	313.02	314.03	2.62	0.34
Nitrosulfathiazole	284.99	284.99	285.99	2.77	10.98

presents the predicted decomposition products based on mass spectral data using software linked to a chemical database.

Figure 5 illustrates the degradation pathway of STZ sodium salt during NTP treatment. Seven species of intermediate by-products were detected, all of which were hydroxyl compounds produced through reactions between ROS radicals in the benzene and thiazole rings or compounds formed by the substitution of radicals with amino groups.

Given that atmospheric air served as the carrier gas, the NTP system concurrently generated significant concentrations of ·OH alongside O₃ [27]. These oxidants exhibit distinct, yet synergistic, reactivities toward the target sulfonamide molecules. While ·OH acts as a powerful, non-selective oxidant primarily responsible for the observed aromatic hydroxylation and the cleavage of the recalcitrant sulfonamide (S-N) bond, O₃ exhibits high electrophilicity, preferentially attacking electron-rich functional groups such as the aniline ring and heterocyclic moieties (e.g., isoxazole or thiazole rings) [15,26].

Furthermore, the dissolution and subsequent decomposition of O₃ at the gas–liquid interface acts as a continuous secondary source of ·OH. Consequently, the distinct intermediate transformation patterns observed in this study are governed by the synergistic interplay between direct O₃-mediated selective electrophilic attacks and ·OH-driven non-selective advanced oxidation.

Ultimately, the changes observed in NTP-treated antibiotics suggest the formation of organic acids (oxalate, acetate, and formate) through oxidation reactions. While the primary degradation of these antibiotics into intermediate organic acids was empirically monitored, their ultimate mineralization into inorganic end products (such as NO₃⁻, NH₄⁺, SO₄²⁻, CO₂, and H₂O) was not directly quantified in this study using TOC or IC. Rather, complete mineralization represents the theoretically projected endpoint of these sequential oxidation pathways, consistent with the established AOP literature. Furthermore, Baran et al. [28] reported that the decomposition of STZ begins with the hydroxylation of the aromatic ring by active radicals, whereas the radicals and sulfonyl groups of the amide and amide groups undergo dissociation or replacement. In this study, we also detected decomposition products resulting from the cleavage of simple molecular bonds, and hydroxyl compounds were formed via radical reactions within the thiazole and benzene rings.

3.4. Comparative Studies for EEO About NTP and Other Processes

Energy consumption is another metric for assessing the utility of sulfonamide antibiotic degradation processes. The EEO values for SMZ sodium salt and STZ sodium salt were calculated as 22.4 and 7.5 kWh/m³/order, respectively. The approximately 3-fold reduction in EEO observed with STZ compared to SMZ aligns closely with their structural disparities. The higher electron density of the thiazole ring in STZ thermodynamically facilitates a more efficient electrophilic attack by ⋅OH, thereby requiring less cumulative energy input per order of degradation. Notably, while SMZ exhibited a higher apparent pseudo-first-order rate constant k_obs during initial exposure, the comprehensive EEO metric, which accounts for the total operational treatment time and the logarithmic reduction ratio log(C₀/C_t), ultimately confirms that STZ’s structural vulnerability yields a more energy-efficient overall degradation profile.

The results also show that for STZ sodium salt, as the initial concentration was higher than that of SMZ sodium salt and the treatment time was longer, the EEO value was higher than that of the other processes. The EEO of the NTP process shows an advantage in energy consumption when treating antibiotics below the detection limit. The EEO values associated with the alternative processes are summarized in

Table 4. Antibiotics removal energy requirement of several processes and NTP.

Antibiotics	Process	EEO (kWh/m3/Order)	Reference
SMZ sodium salt	NTP	22.4	This study
SMZ	Pd-BMCN	831.7	[44]
STZ sodium salt	NTP	7.5	This study
STZ	Catalytic ozonation	53.6~108.8	[45]
	Photocatalytic ozonation	29.7~51.4	[45]
STZ	4-CQDs/BiOCOOH/uCN 50 W (LED lamp)	364	[41]
STZ	4-CQDs/BiOCOOH/uCN 300 W (Xenon lamp)	885	[41]

.

For SMZ, NTP was clearly less than the EEO value (831.7 kWh/m³/order) of the comparator processes [44]. In the case of STZ, our studies confirmed differences of approximately 364 and 885 kWh/m3/order for processes using LED and Xenon lamps, respectively [41]. The EEO value was too low compared with other processes. The high EEO is due to the lamp’s high power (50 W, 300 W) and long treatment time. The O₃ process also showed a higher EEO than NTP, but it involves the addition of a catalyst [45]. Not adding a catalyst in the NTP process should be considered an important point regarding environmental and economic pollution. Overall, the NTP process is cost-effective and offers superior antibiotic removal efficiency.

3.5. Outlook on NTP Process Treatment

Various residual antibiotics have been reported to be continuously discharged from natural water [46]. This type of natural water has adverse effects on humans due to the presence of various residual antibiotics [46]. Contaminated wastewater (e.g., livestock, pharmaceutical, and hospital wastewater) with high concentrations of sulfonamide antibiotics poses a potential risk of antibiotic resistance to the ecosystem [47]. Thus, the vicious cycle of ecosystem and human survival must be minimized by treating pollutants.

Research on pollutant-reduction processes contributes to environmental, social, and economic development from a 3Ps perspective (people, planet, and profit). Although various processes exist for developing AOP technology, the NTP process was used in this study to address the aforementioned vicious cycle. The experimental results supported the applicability of the proposed method to real processes, demonstrating that sulfonamide antibiotics can be reduced with high elimination efficiency (>99.9%). Thus, the NTP process can reduce environmentally relevant concentrations of antibiotics and help create sustainable aquatic environments.

Moreover, in previous studies, NTP process treatment could also provide additional benefits, such as economic benefits [19], reduced toxicity [11,15], pretreatment [48], and the possibility of combination processes, such as biochar and membranes [16,17,18,20,38,42]. However, the NTP still lacks research on scaling-up tests. While this study establishes robust fundamental baseline kinetics, transitioning NTP technology toward field-scale commercialization necessitates overcoming several critical engineering hurdles. First, maintaining techno-economic viability EEO at larger treatment volumes is challenging; as reactor dimensions scale, gas–liquid mass transfer efficiencies often diminish, requiring highly optimized hydrodynamic designs to prevent increased operational costs. Second, the long-term material stability of the plasma electrodes must be validated. Continuous operation in humid, high-voltage environments can lead to electrode passivation or dielectric degradation, thereby significantly increasing maintenance overhead. Third, as previously noted, authentic wastewater matrices contain competitive ROS scavengers (e.g., dissolved organic matter and background alkalinity) that inherently attenuate target degradation efficiencies relative to controlled laboratory matrices. Finally, future scale-up efforts must transition from batch reactors to continuous-flow operations to mitigate bubbling-induced evaporation and establish true hydraulic steady-state parameters. Addressing these multifaceted scaling variables remains the critical frontier for the practical deployment of NTP advanced oxidation systems.

It should also be noted that all degradation experiments were conducted in distilled water. In real wastewater matrices, the presence of radical scavengers such as carbonate/bicarbonate ions, dissolved organic matter (DOM), and other coexisting solutes would compete with target contaminants for reactive oxygen species (ROS), potentially reducing degradation efficiency and increasing the electrical energy per order (EEO) values [32]. This non-target scavenging is expected to attenuate overall degradation efficiency and, correspondingly, increase the operational EEO under field conditions. Consequently, future investigations utilizing authentic wastewater or complex synthetic matrices containing representative scavengers are warranted to fully assess the practical scalability of this NTP treatment. Also, studies are needed to remove non-degradable pollutants through pilot or full-scale research for field applications and in-depth examinations.

4. Conclusions

This study validates a catalyst-free, air-based non-thermal plasma (NTP) system as a highly effective and energetically favorable advanced oxidation process for sulfonamide degradation. The system achieved 99.9% removal of SMZ (320 µg/L) and STZ (600 µg/L), exhibiting apparent pseudo-first-order rate constants of 0.0731 h⁻¹ and 0.0276 h⁻¹, respectively. A primary advantage of this fundamental configuration is its energy efficiency; the system required EEO inputs of only 22.4 and 7.5 kWh/m³, demonstrating strong thermodynamic viability without the need for external chemical dosing. Mechanistic evaluation by LC-MS/MS confirmed that the parent compounds were transformed into intermediate organic by-products via targeted ROS attack. Although complete mineralization into inorganic species (NO₃⁻, NH₄⁺, SO₄²⁻, CO₂, and H₂O, etc.) remains a theoretically projected endpoint requiring further empirical validation, the established degradation kinetics and energy metrics presented herein confirm that NTP is a highly practical, operationally simple mechanism for mitigating recalcitrant pharmaceutical pollutants.