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Haiyang Lin Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Yingying Sun Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Bingying Hu Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Jinjun Fang Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Zhen Ge Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Zhisheng He Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Yang Wei Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, School of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China

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Abstract

SZJ-1207 is a natural product extracted from Stephanotis mucronata (Blanco) Merr which has significant antidepressant effects in various depression mouse models, without obvious acute toxicity or sedative-hypnotic side effects. The aim of this study was to preliminarily clarify the pharmacokinetic characteristics of SZJ-1207 in rats after a single intragastric and intravenous administration. In this study, sensitive and reliable UPLC-MS/MS quantification methods were established and then successfully applied to the pharmacokinetic study of SZJ-1207 in rats. The linear range of SZJ-1207 were 0.5–400 ng mL−1 in plasma, feaces, bile and 20–4,000 ng mL−1 in urine, respectively (r > 0.99). All methods met the requirements of ICH M10. The results of pharmaconetic study showed that Cmax, AUC(0-t) and AUC(0-∞) had linear relationships with the administered doses in the range of 0.5–4.5 mg kg−1. There was a significant gender difference in the AUC (0-t) of 0.5 and 1.5 mg kg−1 and Cmax of 1.5 mg kg−1 after ig (P < 0.05). The excretion rates of SZJ-1207 were 8.46 ± 4.82% in feces, 1.89 ± 1.08% in urine, and 0.179 ± 0.118% in bile. The oral absolute bioavailability of SZJ-1207 was calculated as 64.64%.

Abstract

SZJ-1207 is a natural product extracted from Stephanotis mucronata (Blanco) Merr which has significant antidepressant effects in various depression mouse models, without obvious acute toxicity or sedative-hypnotic side effects. The aim of this study was to preliminarily clarify the pharmacokinetic characteristics of SZJ-1207 in rats after a single intragastric and intravenous administration. In this study, sensitive and reliable UPLC-MS/MS quantification methods were established and then successfully applied to the pharmacokinetic study of SZJ-1207 in rats. The linear range of SZJ-1207 were 0.5–400 ng mL−1 in plasma, feaces, bile and 20–4,000 ng mL−1 in urine, respectively (r > 0.99). All methods met the requirements of ICH M10. The results of pharmaconetic study showed that Cmax, AUC(0-t) and AUC(0-∞) had linear relationships with the administered doses in the range of 0.5–4.5 mg kg−1. There was a significant gender difference in the AUC (0-t) of 0.5 and 1.5 mg kg−1 and Cmax of 1.5 mg kg−1 after ig (P < 0.05). The excretion rates of SZJ-1207 were 8.46 ± 4.82% in feces, 1.89 ± 1.08% in urine, and 0.179 ± 0.118% in bile. The oral absolute bioavailability of SZJ-1207 was calculated as 64.64%.

1 Introduction

Depression severely impairs psychosocial functioning and quality of life, which places a huge burden on patients and their families. Current medication treatments show important limitations, such as slow action onset and adverse side effects. They do not always lead to positive outcomes and in fact, about 30–40% of the patients have complete remission after a course of treatment. 30% of the patients still show residual symptoms with the increasing risk of recurrence, which affects social function after significant clinical response [1].

Complementary and alternative medicine is becoming more popular globally [2]. About 16–44% of patients with mental illnesses use complementary and alternative medicines [3], and a significant majority of them suffer from depression [4]. Chinese herbal medicine (CHM) is the most popular ajunct as antidepressant in China [5]. A large number of people believe that CHM has certain advantages and potential in the prevention and treatment of diseases due to its clinical application for years [6]. Some studies have shown that CHM monotherapy is superior to placebos [7]. Compared with antidepressants alone, the combination treatment of CHM and first-line antidepressants can significantly improve efficacy and reduce the side effects [8].

Previous studies have found that many natural products with antidepressant activity have steroid structures, such as Lilium brownii var. viridulum saponins [9], gypenosides [10], ginsenoside [11], and Panax notoginseng saponins [12], which suggest that natural products with steroidal structures may have similar effect. SZJ-1207 is a natural antidepressant product extracted from the dried stems of Stephanotis mucronata (Blanco) Merr. Sp. Blancoanae with a steroid structure exhibited in Fig. 1. Preliminary studies have shown that SZJ-1207 has effects in a variety of depression mouse models, while no obvious acute toxicity and sedative-hypnotic side effects have been observed [13]. The pharmacokinetic property of SZJ-1207 in mice have been studied in our former research, and the results revealed that this compound had rapid, fairish absorption and fast elimination [14]. However, SZJ-1207 may have different pharmacokinetic characteristics in species. Clarifying the pharmacokinetic and excretion characteristics of SZJ-1207 in rats can provide more data to support the further development of SZJ-1207.

Fig. 1.
Fig. 1.

The structure of SZJ-1207

Citation: Acta Chromatographica 2024; 10.1556/1326.2024.01221

2 Materials and methods

2.1 Chemicals and reagents

SZJ-1207 (purity = 99.53%) and Deacylmetaplexigenin (DMP, purity = 98.0%) were provided by the Natural Medicine Research Group of Hangzhou Medical College. Methyl tert-butyl ether (MTBE) and pure water were purchased from TEDIA (USA) and Watsons (China), respectively. 0.9% saline and sodium heparin were purchased from Biosharp (China). UPLC-grade methanol, and acetonitrile were purchased from Merck (Germany). Sutent 50 was from Virbac (France). Sodium carboxymethyl cellulose (CMC-Na) was purchased from Macklin (China). Ammonia solution was purchased from Aladdin (China).

2.2 Experimental animals

Sprague Dawley rats (body weight range, 220 ± 20 g), half male and half female, were purchased from Zhejiang Center of Laboratory Animals (animal license number, SYXK (Zhejiang, China) 2019–0002). Only drinking water (no food) was provided 12 h before the experiment. The animal experiments were performed in accordance with the Guidelines for the Care and Use of Laboratory Animals, and the study protocols were approved by Institutional Animal Care and Use Committee, ZJCLA (Approval number: ZJCLA-IACUC-20010165).

2.3 Drug administration

Based on the effective dose of 1.0 mg kg−1 of SZJ-1207 in the pharmacodynamic study in C57BL/6 mice, the doses for pharmacokinetic study in SD rats were obtained. In this study, 24 rats were randomly divided equally into 4 groups with respect to weight and gender. Three groups were intragastrically administered (ig) with 0.5, 1.5, 4.5 mg kg−1 of SZJ-1207 in 0.5% carbox-methylcellulose sodium, respectively. The fourth group was administered intravenously with 1.5 mg kg−1 of SZJ-1207 in saline (containing 0.1% methanol).

In the excretion study, 6 rats were ig with 1.5 mg kg−1 of SZJ-1207 to collect urine and feces samples. Another 6 rats were treated with the same dose to collect bile samples.

2.4 Sample collection and preparation

In pharmacokinetic study, blood samples were collected by jugular vein into heparinized tubes at 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 h after ig administration, and at 0, 0.08, 0.17, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 h after the tail vein administration. Then, each blood sample was immediately centrifuged at 8,000 rpm, 4 °C for 5 min. The aliquot of plasma was transferred into another tube and stored at −80 °C until analysis.

In excretion study, each rat was placed alone in metabolic cage after ig. Urine samples were collected at 0–0.5, 0.5–1, 1–3, 3–6, 6–12, 12–24 h with volume recorded. Feces samples were collected at 0–2, 2–4, 4–6, 6–12, and 12–24 h. The feces were dried and ground into powder with weight recorded. 10 mg of feces was mixed with 100 μL of saline, vortexed for 3 min and sonicated for 15 min to obtain fecal homogenate samples. The samples were stored at −80 °C.

After the rats were anesthetized with Sutent 50, bile duct cannulation was performed. Rats were ig with SZJ-1207 upon awakening. Bile was collected at 0–0.5, 0.5–1, 1–3, 3–6, 6–12, and 12–24 h and the volume was recorded. Samples were stored at −80 °C for analysis.

SZJ-1207 was extracted from matrices with a liquid-liquid extraction method. 10 μL DMP (25 ng mL−1 for plasma, 50 ng mL−1 for bile and feces, 200 ng mL−1 for urine) was added into 50 μL samples and vortexed for 1 min. 10 μL 2.5% ammonia (except plasma) and 400 μL MTBE were added, vortexed for 3 min, centrifuged for 5 min (4,000 rpm, 4 °C). The supernatant was separated and dried with N2, and the residue was re-dissolved with 100 μL of 30% acetonitrile. After centrifugation for 10 min (13,000 rpm, 4 °C), the supernatant was analyzed by UPLC-MS/MS.

2.5 Instruments and conditions

The AB SCIEX API 5500 Triple Quad UPLC-MS/MS System was used for SZJ-1207 analysis. The chromatographic separation was carried out at 40 °C using a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm).

The mobile phase consisted of water (A) and acetonitrile (B). The flow rate was 0.3 mL min−1. The isocratic elution procedure for plasma analysis was 0–3 min: 50% B. Gradient elution program for excretions analysis was set as follows: 0–0.8 min, 20% B; 0.8–1 min, 20–50% B; 1–1.6 min, 50% B; 1.6–1.7 min, 50–90% B; 1.7–3 min, 90% B; 3–3.1 min, 90–20% B; 3.1–4 min, 20% B. The injection volume was 10 μL.

Quantification was performed in negative mode. The dominating mass spectrometer parameters are shown in Table 1. The ion source parameters were as follows: source temperature, 550 °C; ion spray voltage, −4,500 V; curtain gas, 35 psi; collision gas, 8 psi. And the product ion mass spectra in negative mode are shown in Fig. 2.

Table 1.

Ion pairs, declustering potential, collision energy, and collision cell exit potential of SZJ-1207 and DMP

CompoundQ1 → Q3 (m/z)Declustering potential (V)Collision energy (V)Collision cell exit potential (V)
SZJ-1207381.4 → 245.1−206−39−18
DMP379.3 → 343.3 (for plasma samples)−180−27−10
DMP379.3 → 221.2 (for excretion samples)−180−35−10
Fig. 2.
Fig. 2.

Product ion mass spectra of SZJ-1207 (A) and DMP (B)

Citation: Acta Chromatographica 2024; 10.1556/1326.2024.01221

2.6 Method validation

The validation of the method was complying with ICH M10 [15].

2.7 Data analysis and statistics

UPLC-MS/MS data were obtained from Analyst software (version 1.6.3) and analyzed by MultiQuant (version 3.0.2) and Excel 2019. Pharmacokinetic parameters were calculated by non-compartmental analysis applying Phoenix WinNonlin software (version 8.1.0). Dose proportionality assessment was performed with confidence interval based on the power model approach [16]. R 4.2 was used for the statistical analysis of t test and linear regression. The data were represented as mean ± SD. The p value was corrected by the Benjamini–Hochberg false discovery rate (BH-FDR) and p < 0.05 was considered statistically significant difference.

3 Results

3.1 Method validation

All contents of method validation met the requirements.

3.1.1 Selectivity and specificity

In the blank plasma, feces, urine and bile samples, no endogenous interference was observed at the retention time of SZJ-1207 and DMP, and the peak shapes of the two components to be measured in plasma, feces, urine, and bile were good. The chromatograms of blank samples, blank samples containing SZJ-1207 and DMP are shown in Figs 3 and 4.

Fig. 3.
Fig. 3.

Representative chromatograms of SZJ-1207 (A) and DMP (B) for blank matrix samples.

a: plasma, b: urine, c: feces, d: bile

Citation: Acta Chromatographica 2024; 10.1556/1326.2024.01221

Fig. 4.
Fig. 4.

Representative chromatograms of SZJ-1207 (A) and DMP (B) for LLOQ samples.

a: plasma, b: urine, c: feces, d: bile

Citation: Acta Chromatographica 2024; 10.1556/1326.2024.01221

3.1.2 Linearity and LLOQ

Linearity was analyzed by the weighted regression method (1/x2) of peak area ratios of SZJ-1207 to DMP versus actual concentrations. The calibration curves (n = 7) were prepared by spiking blank samples with standard solution of SZJ-1207 and DMP. Final concentrations of the calibration standards were 0.5, 1, 5, 30, 100, 300, 400 ng mL−1 in rat feces, bile and plasma, 20, 40, 100, 400, 2,000, 3,200, 4,000 ng mL−1 in rat urine. The correlation coefficient (n = 3) was found to be >0.99, and within the acceptable limits (Table 2).

Table 2.

The result of linear regression equation and LLOQ determination

MatricesRegression equationLinear Range (ng mL−1)Correlation coefficient (r)
Uriney = 2.65x+0.27220–4,0000.9943
Fecesy = 0.891x+0.004650.5–4000.9959
Biley = 0.213x+0.004210.9979
plasmay = 0.253x+0.009770.9958

Signal-to-noise ratios of Lower limit of quantification (LLOQ) in all matrices were >5.

3.1.3 Precision and accuracy

The intra-batch and inter-batch precision and accuracy are shown in Table 3. The accuracy and precision of within-batch and between-batch were <15% of the nominal values. This indicated that the method was accurate and precise over the range of the assay.

Table 3.

The results of precision and accuracy

MatricesConcentration (ng mL−1)Intra-batch (n = 6)Inter-batch (n = 18)
RE (Accuracy, %)Precision (RSD, %)RE (Accuracy, %)Precision (RSD, %)
Urine60−1.66.7−2.26.2
30014.96.210.06.9
3,000−0.112.6−5.15.1
Feces1.513.35.813.17.2
2013.25.312.94.9
3207.43.94.34.8
Bile1.5−0.4111.43.911.6
206.94.46.54.8
3201.62.10.74.4
Plasma1.5−5.78.8−4.46.8
200.54.42.15.3
320−3.91.1−1.72.4

3.1.4 Extraction recovery and matrix effect

The extraction recoveries of SZJ-1207 in the low, medium, and high QC samples ranged from 77.9 to 94.6%. The same evaluation was performed on DMP, and no significant peak area differences were detected. Thus, it was demonstrated that the matrix effect was negligible for the assay (Table 4).

Table 4.

Extraction recovery and matrix Effect

MatricesConcentration (ng mL−1)Extraction recoveryMatrix effect
Mean (%)RSD (%)Mean (%)RSD (%)
Urine6077.95.9110.73.4
30086.34.2
3,00092.11.7132.714.9
Feces1.588.35.098.36.3
2089.35.3
32091.63.9102.24.6
Bile1.594.67.1104.26.6
2079.14.2
32082.12.398.04.8
Plasma1.5108.01.6100.22.6
2086.25.8
32085.61.296.72.3

3.1.5 Stability

The stability results of SZJ-1207 under various conditions are listed in Table 5. No significant analyte reduction was observed during the short-term (4 h for excretions, 3 h for plasma), post-treatment (at 4 °C for 24 h in the autosampler), freeze-thaw cycles from −20 °C to 20–25 °C (3 cycles for excretions, 2 cycles for plasma), long-term experiments (−80 °C for 168 d). Ten-fold dilution test indicated that the analytes were stable under the tested conditions.

Table 5.

Stability of SZJ-1207 under different conditions

MatricesConcentration (ng mL−1)Short-term (Room Temperature)Post-preparation (4 °C, 24 h)Freeze-thaw CyclesLong-term (−80 °C, 168 d)
RE (%)RSD (%)RE (%)RSD (%)RE (%)RSD (%)RE (%)RSD (%)
Urine60−2.38.1−0.425.2−12.58.0−6.29.2
3,000−9.96.5−9.03.2−14.13.0−11.25.5
Feces1.511.97.713.19.514.03.611.18.7
3206.06.92.93.74.53.49.93.1
Bile1.51.04.912.413.31.012.6−4.78.5
320−2.93.3−5.62.9−4.54.6−6.93.1
Plasma1.51.63.85.22.7−5.43.8−11.02.2
32010.17.58.83.07.70.96.71.3

3.2 Pharmacokinetic study of SZJ-1207 in rats

The average plasma concentration-time curves of SZJ-1207 are shown in Fig. 5, and the main pharmacokinetic parameters are shown in Table 6. As shown in Fig. 5, SZJ-1207 exhibited pharmacokinetic characteristics of extremely rapid absorption and elimination in rats.

Table 6.

Main pharmacokinetic parameters of SZJ-1207 in rats (mean ± SD, n = 6)

DoseGendert1/2TmaxCmaxAUC(0-t)AUC(0-∞)Vd/(F)CL/(F)MRT(0-t)
mg kg−1(h)(h)(μg L−1)(μg L−1 h)(μg L−1 h)(L kg−1)(L h−1 kg−1)(h)
0.5 (ig)2.24 ± 1.650.17 ± 0.0141.00 ± 37.3287.47 ± 16.20*98.00 ± 13.71*15.99 ± 11.315.16 ± 0.67*1.86 ± 1.38
1.49 ± 1.930.20 ± 0.0573.50 ± 12.7345.55 ± 8.4848.24 ± 11.7818.86 ± 21.2810.75 ± 2.351.31 ± 1.48
All1.86 ± 1.650.18 ± 0.03107.25 ± 44.6066.51 ± 25.7173.12 ± 29.5617.42 ± 15.327.96 ± 3.421.59 ± 1.31
1.5 (ig)2.90 ± 0.160.14 ± 0.05417.33 ± 70.73*244.74 ± 29.59*264.63 ± 36.88*23.92 ± 2.41*5.74 ± 0.78*1.94 ± 0.31
3.08 ± 0.650.14 ± 0.05249.00 ± 16.70136.30 ± 13.94147.25 ± 19.0045.02 ± 4.6010.31 ± 1.441.87 ± 0.70
All2.99 ± 0.440.14 ± 0.05333.17 ± 103.02190.52 ± 62.89205.94 ± 69.4434.47 ± 12.018.03 ± 2.711.90 ± 0.49
4.5 (ig)2.15 ± 0.460.14 ± 0.051,490.0 ± 395.09748.58 ± 189.53768.19 ± 206.4718.72 ± 4.496.17 ± 1.731.02 ± 0.54
4.68 ± 3.220.20 ± 0.05704.67 ± 141.80469.70 ± 143.81502.20 ± 182.0965.60 ± 53.719.67 ± 2.961.47 ± 0.87
All3.42 ± 2.480.17 ± 0.051,097.3 ± 505.48609.14 ± 214.42635.19 ± 227.0242.16 ± 42.687.92 ± 2.901.25 ± 0.69
1.5 (iv)1.53 ± 0.380.08 ± 0.00873.67 ± 57.57*359.88 ± 41.37*365.26 ± 38.07*9.20 ± 2.954.14 ± 0.41*0.81 ± 0.34*
2.47 ± 2.730.08 ± 0.00646.33 ± 24.19229.55 ± 14.68231.55 ± 15.9822.29 ± 23.626.50 ± 0.460.37 ± 0.07
All2.00 ± 1.820.08 ± 0.00760.00 ± 130.63294.72 ± 76.59298.42 ± 77.7515.75 ± 16.675.32 ± 1.350.59 ± 0.32

Compared with females, * indicates p < 0.05.

After ig administration of 0.5, 1.5 and 4.5 mg kg−1 of SZJ-1207, AUC and Cmax both increased with dose. Cmax were 107.25 ± 44.60, 333.17 ± 103.02, and 1097.33 ± 505.48 μg L−1. AUC(0-t)were 66.51 ± 25.71, 190.52 ± 62.89, 609.14 ± 214.42 μg L−1 h. AUC(0-∞)were 73.12 ± 29.56, 205.94 ± 69.44, 635.19 ± 227.02 μg L−1 h. Linear regression of the logarithm of Cmax, AUC(0-t) and AUC(0-∞) values against the logarithm of the administered doses showed that the 90% confidence intervals of the slopes (β) were 0.88–1.22, 0.85–1.17 and 0.82–1.16, respectively (Fig. 6). The strict 90% confidence interval criteria required that the intervals be entirely within the intervals for Cmax (0.84, 1.16) and AUC (0.90, 1.10), respectively, and thus no clear conclusion could be drawn. The absolute bioavailability of 1.5 mg kg−1 SZJ-1207 in rats given by ig was 64.64%.

Fig. 5.
Fig. 5.

The average plasma concentration-time curves of SZJ-1207 in rats

Citation: Acta Chromatographica 2024; 10.1556/1326.2024.01221

Fig. 6.
Fig. 6.

Linear relationship between pharmacokinetic parameters and dose

Citation: Acta Chromatographica 2024; 10.1556/1326.2024.01221

Comparing pharmacokinetic parameters between different genders, it was found that SZJ-1207 had higher exposure levels and lower clearance rate in male rats. Especially, there were significant differences between genders in AUC and CL at doses of both 0.5 and 1.5 mg kg−1 (p < 0.05) and in Cmax at a dose of 1.5 mg kg−1 (p < 0.05). The absence of gender-stratified informations for many medications raises the concerns that gender differences in pharmacokinetics may be widespread and of clinical significance [17]. These may be primarily due to the expression differences of hepatic metabolic enzymes between genders, resulting in differences of drug metabolism and drug exposure in vivo. Thus, the gender differences of SZJ-1207 reflected in this study should be paid attention to.

In addition, a small increase in SZJ-1207 concentration was observed at the end of the elimination phase in the plasma concentration-time curve. It is hypothesized that enterohepatic circulation of SZJ-1207 led to drug reabsorption into blood.

3.3 Excretion study in rats

The results are shown in Tables 7 and 8. Only a small portion of unchanged SZJ-1207 was excreted via the renal, fecal and biliary routes. And the cumulative excretion rates were 1.89 ± 1.08%, 8.46 ± 4.82% and 0.179 ± 0.118%, respectively. The total excretion of SZJ-1207 was less than 20% of the administered dose. It was promoted that most of SZJ-1207 was metabolized in rats and further studies should be carried out to clarify how SZJ-1207 is disposed in vivo.

Table 7.

Excretion characteristics of SZJ-1207 via urine and bile

Time (h)Urine excretion (μg)Urine excretion rate (%)Bile excretion (μg)Bile excretion rate (%)
Mean ± SD (n = 6)Mean ± SD (n = 6)
0–0.51.80 ± 1.600.523 ± 0.4680.261 ± 0.2240.0711 ± 0.0619
0.5–11.60 ± 0.9630.466 ± 0.2710.166 ± 0.09760.0448 ± 0.0253
1–30.636 ± 0.1530.188 ± 0.03910.160 ± 0.04610.0432 ± 0.0115
3–60.358 ± 0.1340.107 ± 0.04210.0534 ± 0.04790.0143 ± 0.0125
6–121.22 ± 0.6020.373 ± 0.2010.0187 ± 0.02460.00502 ± 0.00653
12–240.773 ± 0.2000.231 ± 0.06310.003280.000877
Total6.39 ± 3.651.89 ± 1.080.662 ± 0.4400.179 ± 0.118
Table 8.

Excretion characteristic of feces

Time (h)Feces excretion (μg)Feces excretion rate (%)
Mean ± SD (n = 6)
0–20.156 ± 0.1280.0465 ± 0.0376
2–40.324 ± 0.2420.0941 ± 0.0676
4–62.32 ± 2.330.665 ± 0.647
6–1221.7 ± 10.36.51 ± 3.19
12–243.80 ± 2.801.14 ± 0.874
Total28.3 ± 15.78.46 ± 4.82

4 Conclusion

In this study, sensitive, robust, and reliable UPLC-MS/MS methods were established and validated for determination of SZJ-1207 in different matrices. The methods successfully applied to quantitation of the compound in rat plasma, feces, urine, and bile samples.

SZJ-1207 presented pharmacokinetic characteristics of extremely rapid absorption and elimination in rats. Compared with in female rats, SZJ-1207 showed higher exposure levels and lower clearance rate in male rats. The bioavailability of 1.5 mg kg−1 SZJ-1207 in rats given by ig was 64.64%. To improve pharmacokinetic properties of this compound, pharmaceutic approches could be employed to prolong its residence time in vivo and to improve its druggability.

SZJ-1207 exhibited lower levels in excretion samples, indicating that it underwent extensive metabolism in rats. So, structure modification could be another means to promote its druggability.

Acknowledgements

This work was supported by Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province (2019E10021), Medical and Health Science and Technology Program of Zhejiang Provincial Health Commission of China (2022KY725, 2021KY633) and Zhejiang Provincial Key R&D Program of China (2022C03097).

Abbreviations

DMP

deacylmetaplexigenin

LLOQ

lower limit of quantification

CHM

Chinese herbal medicine

MTBE

Methyl tert-butyl ether

ig

intragastrically administration

NA

not applicable

RSD

relative standard deviation

RE

relative error

h

hour

min

minute

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    Hsu, M. C.; Creedy, D.; Moyle, W.; Venturato, L.; Tsay, S. L. Use of complementary and alternative medicine among adult patients for depression in Taiwan. J. Affect Disord. 2008, 111(2-3), 3605. https://doi.org/10.1016/j.jad.2008.03.010.

    • Search Google Scholar
    • Export Citation
  • 6.

    Guo, Y.; Wang, T.; Chen, W.; Kaptchuk, T. J.; Li, X.; Gao, X.; Yao, J.; Tang, X.; Xu, Z. Acceptability of traditional Chinese medicine in Chinese people based on 10-year's real world study with multiple big data mining. Front Public Health 2021, 9, 811730. https://doi.org/10.3389/fpubh.2021.811730.

    • Search Google Scholar
    • Export Citation
  • 7.

    Li, L. T.; Wang, S. H.; Ge, H. Y.; Chen, J.; Yue, S. W.; Yu, M. The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) and fluoxetine on post-stroke depression. J. Altern. Complem Med. 2008, 14(7), 8416. https://doi.org/10.1089/acm.2008.0010.

    • Search Google Scholar
    • Export Citation
  • 8.

    Liu, L. Y.; Feng, B.; Chen, J.; Tan, Q. R.; Chen, Z. X.; Chen, W. S.; Wang, P. R.; Zhang, Z. J. Herbal medicine for hospitalized patients with severe depressive episode: a retrospective controlled study. J. Affect Disord. 2015, 170, 717. https://doi.org/10.1016/j.jad.2014.08.027.

    • Search Google Scholar
    • Export Citation
  • 9.

    Du, H.; Wang, K.; Su, L.; Zhao, H.; Gao, S.; Lin, Q.; Ma, X.; Zhu, B.; Dong, X.; Lou, Z. Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression. J. Pharmaceut Biomed. 2016, 128, 469479. https://doi.org/10.1016/j.jpba.2016.06.019.

    • Search Google Scholar
    • Export Citation
  • 10.

    Cao, L. H.; Zhao, Y. Y.; Bai, M.; Geliebter, D.; Geliebter, J.; Tiwari, R.; He, H. J.; Wang, Z. Z.; Jia, X. Y.; Li, J.; Li, X. M.; Miao, M. S. Mechanistic studies of gypenosides in microglial state transition and its implications in depression-like behaviors: role of TLR4/MyD88/NF-kappaB signaling. Front Pharmacol. 2022, 13, 838261. https://doi.org/10.3389/fphar.2022.838261.

    • Search Google Scholar
    • Export Citation
  • 11.

    Zhang, J. H.; Yang, H. Z.; Su, H.; Song, J.; Bai, Y.; Deng, L.; Feng, C. P.; Guo, H. X.; Wang, Y.; Gao, X.; Gu, Y.; Zhen, Z.; Lu, Y. Berberine and ginsenoside Rb1 ameliorate depression-like behavior in diabetic rats. Am. J. Chin. Med 2021, 49(5), 11951213. https://doi.org/10.1142/S0192415X21500579.

    • Search Google Scholar
    • Export Citation
  • 12.

    Xie, W.; Meng, X.; Zhai, Y.; Zhou, P.; Ye, T.; Wang, Z.; Sun, G.; Sun, X. Panax notoginseng saponins: a review of its mechanisms of antidepressant or anxiolytic effects and network analysis on phytochemistry and pharmacology. Molecules 2018, 23(4). https://doi.org/10.3390/molecules23040940.

    • Search Google Scholar
    • Export Citation
  • 13.

    Yiping, Y.; Xiaoyu, L.; Yewei, Y.; Zhengrong, Z.; Fengyang, C.; Shifang, X.; Wenhai, H. Application of antidepressant compound in preparation of antidepressant drugs and antidepressant health-care foods, 2018. https://go.exlibris.link/qkGRd0YK.

    • Search Google Scholar
    • Export Citation
  • 14.

    Qi, D.; Sun, Y.; Hu, B.; An, H.; Lin, H.; Fang, J.; Wei, Y. UPLC-MS/MS analysis of SZJ-1207 in mouse plasma and brain and application in pharmacokinetic studies. Acta Chromatogr. 2023. https://doi.org/10.1556/1326.2022.01102.

    • Search Google Scholar
    • Export Citation
  • 15.

    ICH Expert Group. Bioanalytical Method Validation and Study Sample Analysis M10, 2020.

  • 16.

    Ming, Z.; Jin, Y.; Minji, W. Confidence interval method for linear pharmacokinetic characterization. Chin. J. Clin. Pharmacol. 2015, 31, 23840. https://link.cnki.net/doi/10.13699/j.cnki.1001-6821.2015.03.024.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zucker, I.; Prendergast, B. J. Sex differences in pharmacokinetics. Sex Gend. Effects Pharmacol. 2023, 2539. https://doi.org/10.1007/164_2023_669.

    • Search Google Scholar
    • Export Citation
  • 1.

    Zhang, Y.; Long, Y.; Yu, S.; Li, D.; Yang, M.; Guan, Y.; Zhang, D.; Wan, J.; Liu, S.; Shi, A.; Li, N.; Peng, W. Natural volatile oils derived from herbal medicines: a promising therapy way for treating depressive disorder. Pharmacol. Res. 2021, 164, 105376. https://doi.org/10.1016/j.phrs.2020.105376.

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    • Export Citation
  • 2.

    Tindle, H. A.; Davis, R. B.; Phillips, R. S. Trends in use of complementary and alternative medicine by US adults: 1997–2002. Altern. Ther. Health M 2005, 11(1), 429. https://pubmed.ncbi.nlm.nih.gov/15712765/.

    • Search Google Scholar
    • Export Citation
  • 3.

    Purohit, M. P.; Wells, R. E.; Zafonte, R. D.; Davis, R. B.; Phillips, R. S. Neuropsychiatric symptoms and the use of complementary and alternative medicine. Pm&R 2013, 5(1), 2431. https://doi.org/10.1016/j.pmrj.2012.06.012.

    • Search Google Scholar
    • Export Citation
  • 4.

    Freeman, M. P.; Fava, M.; Lake, J.; Trivedi, M. H.; Wisner, K. L.; Mischoulon, D. Complementary and alternative medicine in major depressive disorder: the American Psychiatric Association Task Force report. J. Clin. Psychiat 2010, 71(6), 66981. https://doi.org/10.4088/JCP.10cs05959blu.

    • Search Google Scholar
    • Export Citation
  • 5.

    Hsu, M. C.; Creedy, D.; Moyle, W.; Venturato, L.; Tsay, S. L. Use of complementary and alternative medicine among adult patients for depression in Taiwan. J. Affect Disord. 2008, 111(2-3), 3605. https://doi.org/10.1016/j.jad.2008.03.010.

    • Search Google Scholar
    • Export Citation
  • 6.

    Guo, Y.; Wang, T.; Chen, W.; Kaptchuk, T. J.; Li, X.; Gao, X.; Yao, J.; Tang, X.; Xu, Z. Acceptability of traditional Chinese medicine in Chinese people based on 10-year's real world study with multiple big data mining. Front Public Health 2021, 9, 811730. https://doi.org/10.3389/fpubh.2021.811730.

    • Search Google Scholar
    • Export Citation
  • 7.

    Li, L. T.; Wang, S. H.; Ge, H. Y.; Chen, J.; Yue, S. W.; Yu, M. The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) and fluoxetine on post-stroke depression. J. Altern. Complem Med. 2008, 14(7), 8416. https://doi.org/10.1089/acm.2008.0010.

    • Search Google Scholar
    • Export Citation
  • 8.

    Liu, L. Y.; Feng, B.; Chen, J.; Tan, Q. R.; Chen, Z. X.; Chen, W. S.; Wang, P. R.; Zhang, Z. J. Herbal medicine for hospitalized patients with severe depressive episode: a retrospective controlled study. J. Affect Disord. 2015, 170, 717. https://doi.org/10.1016/j.jad.2014.08.027.

    • Search Google Scholar
    • Export Citation
  • 9.

    Du, H.; Wang, K.; Su, L.; Zhao, H.; Gao, S.; Lin, Q.; Ma, X.; Zhu, B.; Dong, X.; Lou, Z. Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression. J. Pharmaceut Biomed. 2016, 128, 469479. https://doi.org/10.1016/j.jpba.2016.06.019.

    • Search Google Scholar
    • Export Citation
  • 10.

    Cao, L. H.; Zhao, Y. Y.; Bai, M.; Geliebter, D.; Geliebter, J.; Tiwari, R.; He, H. J.; Wang, Z. Z.; Jia, X. Y.; Li, J.; Li, X. M.; Miao, M. S. Mechanistic studies of gypenosides in microglial state transition and its implications in depression-like behaviors: role of TLR4/MyD88/NF-kappaB signaling. Front Pharmacol. 2022, 13, 838261. https://doi.org/10.3389/fphar.2022.838261.

    • Search Google Scholar
    • Export Citation
  • 11.

    Zhang, J. H.; Yang, H. Z.; Su, H.; Song, J.; Bai, Y.; Deng, L.; Feng, C. P.; Guo, H. X.; Wang, Y.; Gao, X.; Gu, Y.; Zhen, Z.; Lu, Y. Berberine and ginsenoside Rb1 ameliorate depression-like behavior in diabetic rats. Am. J. Chin. Med 2021, 49(5), 11951213. https://doi.org/10.1142/S0192415X21500579.

    • Search Google Scholar
    • Export Citation
  • 12.

    Xie, W.; Meng, X.; Zhai, Y.; Zhou, P.; Ye, T.; Wang, Z.; Sun, G.; Sun, X. Panax notoginseng saponins: a review of its mechanisms of antidepressant or anxiolytic effects and network analysis on phytochemistry and pharmacology. Molecules 2018, 23(4). https://doi.org/10.3390/molecules23040940.

    • Search Google Scholar
    • Export Citation
  • 13.

    Yiping, Y.; Xiaoyu, L.; Yewei, Y.; Zhengrong, Z.; Fengyang, C.; Shifang, X.; Wenhai, H. Application of antidepressant compound in preparation of antidepressant drugs and antidepressant health-care foods, 2018. https://go.exlibris.link/qkGRd0YK.

    • Search Google Scholar
    • Export Citation
  • 14.

    Qi, D.; Sun, Y.; Hu, B.; An, H.; Lin, H.; Fang, J.; Wei, Y. UPLC-MS/MS analysis of SZJ-1207 in mouse plasma and brain and application in pharmacokinetic studies. Acta Chromatogr. 2023. https://doi.org/10.1556/1326.2022.01102.

    • Search Google Scholar
    • Export Citation
  • 15.

    ICH Expert Group. Bioanalytical Method Validation and Study Sample Analysis M10, 2020.

  • 16.

    Ming, Z.; Jin, Y.; Minji, W. Confidence interval method for linear pharmacokinetic characterization. Chin. J. Clin. Pharmacol. 2015, 31, 23840. https://link.cnki.net/doi/10.13699/j.cnki.1001-6821.2015.03.024.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zucker, I.; Prendergast, B. J. Sex differences in pharmacokinetics. Sex Gend. Effects Pharmacol. 2023, 2539. https://doi.org/10.1007/164_2023_669.

    • Search Google Scholar
    • Export Citation
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Senior editors

Editor(s)-in-Chief: Kowalska, Teresa (1946-2023)

Editor(s)-in-Chief: Sajewicz, Mieczyslaw

Editors(s)

  • Danica Agbaba (University of Belgrade, Belgrade, Serbia)
  • Łukasz Komsta (Medical University of Lublin, Lublin, Poland)
  • Ivana Stanimirova-Daszykowska (University of Silesia, Katowice, Poland)
  • Monika Waksmundzka-Hajnos (Medical University of Lublin, Lublin, Poland)

Editorial Board

  • R. Bhushan (The Indian Institute of Technology, Roorkee, India)
  • J. Bojarski (Jagiellonian University, Kraków, Poland)
  • B. Chankvetadze (State University of Tbilisi, Tbilisi, Georgia)
  • M. Daszykowski (University of Silesia, Katowice, Poland)
  • T.H. Dzido (Medical University of Lublin, Lublin, Poland)
  • A. Felinger (University of Pécs, Pécs, Hungary)
  • K. Glowniak (Medical University of Lublin, Lublin, Poland)
  • B. Glód (Siedlce University of Natural Sciences and Humanities, Siedlce, Poland)
  • A. Gumieniczek (Medical University of Lublin, Lublin, Poland)
  • U. Hubicka (Jagiellonian University, Kraków, Poland)
  • K. Kaczmarski (Rzeszow University of Technology, Rzeszów, Poland)
  • H. Kalász (Semmelweis University, Budapest, Hungary)
  • K. Karljiković Rajić (University of Belgrade, Belgrade, Serbia)
  • I. Klebovich (Semmelweis University, Budapest, Hungary)
  • A. Koch (Private Pharmacy, Hamburg, Germany)
  • P. Kus (Univerity of Silesia, Katowice, Poland)
  • D. Mangelings (Free University of Brussels, Brussels, Belgium)
  • E. Mincsovics (Corvinus University of Budapest, Budapest, Hungary)
  • Á. M. Móricz (Centre for Agricultural Research, Budapest, Hungary)
  • G. Morlock (Giessen University, Giessen, Germany)
  • A. Petruczynik (Medical University of Lublin, Lublin, Poland)
  • R. Skibiński (Medical University of Lublin, Lublin, Poland)
  • B. Spangenberg (Offenburg University of Applied Sciences, Germany)
  • T. Tuzimski (Medical University of Lublin, Lublin, Poland)
  • Y. Vander Heyden (Free University of Brussels, Brussels, Belgium)
  • A. Voelkel (Poznań University of Technology, Poznań, Poland)
  • B. Walczak (University of Silesia, Katowice, Poland)
  • W. Wasiak (Adam Mickiewicz University, Poznań, Poland)
  • I.G. Zenkevich (St. Petersburg State University, St. Petersburg, Russian Federation)

 

KOWALSKA, TERESA (1946-2023)
E-mail: kowalska@us.edu.pl

SAJEWICZ, MIECZYSLAW
E-mail:msajewic@us.edu.pl

Indexing and Abstracting Services:

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2022  
Web of Science  
Total Cites
WoS
647
Journal Impact Factor 1.9
Rank by Impact Factor

Chemistry, Analytical (Q3)

Impact Factor
without
Journal Self Cites
1.9
5 Year
Impact Factor
1.4
Journal Citation Indicator 0.41
Rank by Journal Citation Indicator

Chemistry, Analytical (Q3)

Scimago  
Scimago
H-index
29
Scimago
Journal Rank
0.28
Scimago Quartile Score

Chemistry (miscellaneous) (Q3)

Scopus  
Scopus
Cite Score
3.1
Scopus
CIte Score Rank
General Chemistry 211/407 (48th PCTL)
Scopus
SNIP
0.549

2021  
Web of Science  
Total Cites
WoS
652
Journal Impact Factor 2,011
Rank by Impact Factor Chemistry, Analytical 66/87
Impact Factor
without
Journal Self Cites
1,789
5 Year
Impact Factor
1,350
Journal Citation Indicator 0,40
Rank by Journal Citation Indicator Chemistry, Analytical 72/99
Scimago  
Scimago
H-index
29
Scimago
Journal Rank
0,27
Scimago Quartile Score Chemistry (miscellaneous) (Q3)
Scopus  
Scopus
Cite Score
2,8
Scopus
CIte Score Rank
General Chemistry 210/409 (Q3)
Scopus
SNIP
0,586

2020
 
Total Cites
650
WoS
Journal
Impact Factor
1,639
Rank by
Chemistry, Analytical 71/83 (Q4)
Impact Factor
 
Impact Factor
1,412
without
Journal Self Cites
5 Year
1,301
Impact Factor
Journal
0,34
Citation Indicator
 
Rank by Journal
Chemistry, Analytical 75/93 (Q4)
Citation Indicator
 
Citable
45
Items
Total
43
Articles
Total
2
Reviews
Scimago
28
H-index
Scimago
0,316
Journal Rank
Scimago
Chemistry (miscellaneous) Q3
Quartile Score
 
Scopus
393/181=2,2
Scite Score
 
Scopus
General Chemistry 215/398 (Q3)
Scite Score Rank
 
Scopus
0,560
SNIP
 
Days from
58
submission
 
to acceptance
 
Days from
68
acceptance
 
to publication
 
Acceptance
51%
Rate

2019  
Total Cites
WoS
495
Impact Factor 1,418
Impact Factor
without
Journal Self Cites
1,374
5 Year
Impact Factor
0,936
Immediacy
Index
0,460
Citable
Items
50
Total
Articles
50
Total
Reviews
0
Cited
Half-Life
6,2
Citing
Half-Life
8,3
Eigenfactor
Score
0,00048
Article Influence
Score
0,164
% Articles
in
Citable Items
100,00
Normalized
Eigenfactor
0,05895
Average
IF
Percentile
20,349
Scimago
H-index
26
Scimago
Journal Rank
0,255
Scopus
Scite Score
226/167=1,4
Scopus
Scite Score Rank
Chemistry (miscellaneous) 240/398 (Q3)
Scopus
SNIP
0,494
Acceptance
Rate
41%

 

Acta Chromatographica
Publication Model Online only
Gold Open Access
Submission Fee none
Article Processing Charge 400 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription Information Gold Open Access
Purchase per Title  

Acta Chromatographica
Language English
Size A4
Year of
Foundation
1988
Volumes
per Year
1
Issues
per Year
4
Founder Institute of Chemistry, University of Silesia
Founder's
Address
PL-40-007 Katowice, Poland, Bankowa 12
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2083-5736 (Online)

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