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BGT-002, a new type of ATP-citrate lyase inhibitor, is a promising therapeutic for treatment of hypercholesterolemia. After an oral administration of BGT-002 to subjects, it underwent extensive metabolism and an acyl monoglucuronide (ZM326E-M2) on 1- carboxylic acid group was the major circulating metabolite. In this study, an LC-MS/MS method was developed and validated for the simultaneous determination of BGT-002 and ZM326E-M2 in plasma and the evaluation of their pharmacokinetic characteristics in humans. After extraction from the plasma by acetonitrile-induced protein precipitation, the analytes were separated on a Waters ACQUITY UPLC® BEH C 18 column using acetonitrile and 2 mM ammonium acetate containing 0.1% formic acid as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) of m/z 501.3→325.4 for ZM326E-M2 and m/z 507.3→331.2 for D 6 -ZM326E-M2, and pseudo-MRM of m/z 325.3→325.3 for BGT-002 and m/z 331.3→331.3 for D 6 -ZM326E, respectively. The method was validated with respect to accuracy, precision, linearity, stability, selectivity, matrix effect, and recovery. The analytical range in human plasma was linear over a concentration range of 0.0500-50.0 μg/mL for BGT-002 and 0.0100-10.0 μg/mL for ZM326E-M2. The pharmacokinetic results showed that after a single oral administration of 100 mg BGT-002, the parent drug was rapidly absorbed with a mean time to peak concentration (t max ) of 1.13 h, compared with BGT-002, the t max (4.00 h) of ZM326E-M2 was significantly delayed. The peak concentration and plasma exposure of ZM326E-M2 were about 14.1% and 19.5% of the parent drug, suggesting that attention should be paid to the safety and efficacy of ZM326E-M2 in clinical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection. Methods: Around 10 mmNH 4 Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis. Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.

Objective: To establish a method for the determination of 5-hydroxy tryptamine (5-HT),adrenalin (AD) and noradrenalin (NA) in human plasma using pre-column derivatization HPLC-MS/MS. Methods Derivatives of the plasma samples were produced with dansyl chloride under pH 10.5,and then extracted and enriched with ethyl acetate. The detected chemicals were separated using Ultimate C₁₈ (50 mm×4.6 mm,5 μm) with acetonitrile-water-formic acid=95∶5∶0.05 ( V∶V∶V ) at 0.2 mL/min. The HPLC-MS//MS system was operated under a multiple reaction monitoring mode (MRM) using the electrospray ionization technique in positive mode., Results: Linear range of the calibration curve appeared in 250-2.5 ng/mL. The method had a less than 9% intra- and inter-assay relative standard deviation ( RSD ),95.44%-109.71% recoveries,and 4.86%-12.81% matrix effects., Conclusion: This method is simple,accurate,and suitable for detection of 5-HT,AD and NA in human plasma., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Objective: To establish a high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) method for determination of warfarin enantiomers in human plasma., Methods: Warfarin enantiomers were extracted with ethyl acetate. The HPLC-MS/MS method used naproxen as internal standard, with methanol : water : formic acid = 85 : 15 : 0.05 as mobile phase, at a flow rate of 0.18 mL/min. R-warfain, S-warfarin and internal standard (IS) were separated on column MS Chiral MS-OD (50 x 2.1 mm, 3 μm). Warfarin enantiomers were protonated with electroapry ionization (ESI) in negative electron ionization mode. The ion pairs being detected were (m/z) 307.2-160.9 (R-warfain and S-warafrin) and (m/z) 228.9 --> 185.1 (IS)., Results: The within-run precision relative standard deviations (RSD) and between-run precision RSD of R-warfarin were 3.2%-5.8% and 2.5%-5.1%, respectively. The method recoveries and extraction recoveries of R-warfarin were (96.1 ± 5. 6)%-(105.4 ± 4.7)% and 80.7%-84.4%, respectively. The matrix effect RSD was less than 10%. The within-run precision RSD and between-run precision RSD of S-warfarin were 3.7%-5.2% and 3.2%-4.8%, respectively. The method recoveries and extraction recoveries of 5-warfarin were (98.3 ± 5.1)%-(103.7 ± 3.8)% and 81.3%-84.6%, respectively. The limit of quantification was 0.1 μg/mL for both analytes., Conclusion: This new method is fully validated with satisfactory accuracy and adequate reproducibility. Therefore, it can be applied for separating and detecting plasma warfarin enantiomers.

Objective: To develop a sensitive and reproducible HPLC-MS/MS method for analyzing dimemorfan in human plasma and urine., Methods: Dimemorfan was extracted from plasma and urine by redistilled ether, with lidocaine serving as the internal standard (IS). The analysis was performed on a column of ultimate C18 (50 mm x 4.6 mm, 5 microm) with the mobile phase consisting of methyl alcohol-water-formic acid = 75:25 : 0.05 at a flow rate of 0. 2 mL/min. Dimemorfan was detected by API 3000 mass spectrometer, with multiple reaction monitoring after protonated with ESI in positive electron ionization mode. The ion pairs being detected were (m/z) 256.4-->155. 3 (dimemorfan) and 235.4-->86.1 (lidocaine), respectively., Results: The regression equation for dimemorfan showed excellent linearity (r = 0.995 7) from 0. 025 to 5.0 ng/mL of plasma with detecting limitation of 0.025 ng/mL and perfect linearity (r = 0.9983) from 0.1 to 20.0 ng/mL of urine with detecting limitation of 0.1 ng/mL. The method recoveries of dimemorfan in plasma and urine were ranging from 103.38% to 106.88% and 90.05% to 101.40%, respectively. The maximum intra-day and inter-day relative standard deviations (RSD) of concentration of dimemorfan were 5.92% and 5. 70% (for plasma), 10.35% and 8.80% (for urine), respectively., Conclusion: This new method was validated to be accurate and sensitive to determinate the concentration of dimemorfan in plasma and urine samples, and can be applied for pharmacokinetic studies of dimemorfan.

Objective: To develop a specific and sensitive method for the determination of probucol in human plasma using HPLC-MS/MS technique., Methods: Probucol were extracted from plasma by ethyl ether: dichloromethane (1:1, V/V), with physcion as an internal standard. The analytes went through the column of ultimate CN (50 mm x 4.6 mm, 5 microm) with mobile phase acetonitrile: water: ammonia water = 97:3:0.05 (adjusted pH = 7.2 with formic acid). Probucol was analyzed with a negative mode. The ion pairs being detected were 515.5-->236.1 (probucol) and 283.0-->239.9 physcion, respectively., Results: The established method was able to determine probucol in human plasma over the range of 2.5-6000 ng/mL, with a method recovery ranging from 93.02% to 104.12%. The intra and inter day variances were below 4.67% and 5.72%., Conclusion: The HPLC-MS/MS method for analyzing probucol was validated. It is sensitive and suitable for pharmacokinetic studies of probucol.

Objective: To develop and validate a normal phase HPLC-MS/MS method for the determination of donepezil enantiomer in human plasma., Methods: Donepezil was extracted from plasma by n-hexane:isopropanol (98:2, V/V) with lidocaine serving as an internal standard. The analytes went through the column of CHIRALCEL OJ-H (250 mm x 4.6 mm, 5 microm) with mobile phase n-hexane:n-propanol:diethylamine (60:40: 0.1, V/V/V). Donepezil enantiomer was determined by API 3000 in MRM mode., Results: The retention time of S-DN and R-DN were 15.56 min and 18.41 min, respectively. The calibration curves were linear in a range from 0.051 to 7.596 ng/mL for S-DN, and from 0.049 to 7.404 ng/mL for R-DN, respectively, both with more than 0.99 correlation coefficients. The relative recovery were 95.10%-103.70% for S-DN and 93.58%-98.00% for R-DN, respectively; the pretreatment recovery were 58.42%-61.08% for S-DN and 53.24%-61.87% for R-DN, respectively; the within-day RSD ranged from 8.35% to 11.28% for S-DN and from 6.78% to 11.58% for R-DN, respectively; the between-day RSD ranged from 5.82% to 9.02% for S-DN and from 6.87% to 9.19% for R-DN, respectively., Conclusion: This normal phase HPLC-MS/MS method is simple, rapid, sensitive and accurate for the determination of donepezil enantiomer in human plasma and is suitable for pharmacokinetic studies of donepezil enantiomers.

Objective: To establish a liquid chromatography tandem mass spectrometry method for the determination of ubenimex in human plasma., Methods: The essay was conducted with an API 3000 HPLC-MS/MS system consisted of a Ultimate C18 column (50 mm x 4.6 mm, 5 microm). The mobile phase consisted of methanol-water-formic acid (70 : 30 : 0.05, V/V/V) at a flow rate of 0.2 mL/min. Granisetron was used as the internal standard. The sample was extracted by solid phase extraction column and was operated under the multiple reaction monitoring mode using the electrospray ionization technique in positive mode., Results: The linear range of ubenimex was 0.4-4000 ng/mL. The limit of quantity was set at 0.4 ng/mL. The within-day and between-day variations were less than 6%., Conclusion: This method for the quantitative determination of ubenimex was proved to be accurate, sensitive, selective and convenient and can be applied in the determination of ubenimex in human plasma.

Objective: To establish a liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the determination of lidocaine (LDC) and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in human plasma. METHODS; The assay was conducted with an API 3000 HPLC-MS/MS system consisted of a Ultimate C18 column (50 x 4.6 mm, 5 microm). The mobile phase consisted of methanol: 5 mmol/ L ammonium acetate (50:50, pH was adjusted to 5.0 by formic acid) and the flow rate was set at 0.2 mL/min. The alkalinized sample was extracted with ethyl acetate. After evaporation of the organic layer, the residue was dissolved in mobile phase and the drug was determined by HPLC-MS/MS using electrospray ionization., Results: The calibration curve was linear in a range from 15.625 to 2000 ng/mL for LDC. Linear calibration curves were obtained in the range of 1.5625 to 200 ng/mL for both for MEGX and GX. The limit of quantification for LDC, MEGX and GX was set at 15.625, 1.5625 and 1.5625 ng/mL., Conclusion: This method for the quantitative determination of lidocaine and its metabolites in human plasma is simple, rapid, sensitive and accurate. Therefore it can be used for the determination of lidocaine and its metabolites in clinical practice.

Objective: To develop a method for detecting penehyclidine hydrochloride (PH) in mouse plasma and tissues using HPLC-MS/MS., Methods: The plasma and tissue samples were extracted with petroleum ether, ethyl ether (70:30). The isolation of PH was achieved on an Allure C18, (50 x 2.1 mm, 5 microm) column, with methanol/5 mmol/L ammonium acetate/triethylamine = 90/10/0.05 (adjusted pH 5.8 by formic acid as mobile phase. Benzhydramine was used as the internal standard., Results: The calibration curves were linear over the range of 0.39-200 ng/mL for plasma and 0.391-100 ng/mL for tissues. The extraction recovered 67.32-70.80% of PH in plasma, 84.99%-89.27% of PH in lung tissues, and 76.86%-81.98% of PH in brain tissues. The HPLC detected 97.66%-99.97% of PH in extracted samples of plasma, 96.55%-101.65% extracted samples of lung and 95.18%-100.21% of extracted samples of brain. The within-day RSD were 1.94%-2.93%, 1.73%-3.70% and 2.35%-2.79% for plasma, lung, and brain, respectively. The between-day RSD were 3.00%-3.85% 2.86%-3.94% and 2.77%-5.00% for plasma, lung, and brain, respectively. Both the long-term and freeze-thaw stabilities were acceptable. The long-term RSD were 1.52%-5.26%, 1.88%-2.93%, and 2.22%-3.76% for plasma, lung, and brain, respectively. The freeze-thaw RSD were 0.38%-3.55%, 2.79%-9.60%, and 1.35%-2.29% for plasma, lung, and brain, respectively., Conclusion: The assay is simple and accurate, with good reproducibility, and can satisfy to the needs of pharmacokinetics and relative bioavailability studies on penehyclidine hydrochloride.

A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of the 10 major components of Da-Cheng-Qi decoction (rhein, emodin, aloe-emodin, chrysophanol, rheochrysidin, naringin, naringenin, hesperidin, magnolol and honokiol) in dog plasma. Plasma samples were spiked with internal standard (ibuprofen), acidified with HCl and extracted twice by liquid-liquid extraction using ethyl acetate. Separation was performed on a YMC-Pack ODS-A C(18) column (5 microm, 150 mm x 4.6 mm) and a C(18) guard column (5 microm, 4.0 mm x 2.0 mm) with methanol-water (92:8, v/v) at a flow rate of 0.3 mL/min. The LC/MS system was operated under the multiple reaction monitoring mode using electrospray ionization in the negative ion mode. All analytes showed good linearity over a wide concentration range (r>0.99). The linear range of the calibration curves was 5000-19.53 ng/mL for rhein; 400-3.13 ng/mL for emodin; 800-3.13 ng/mL for aloe-emodin, chrysophanol, naringin, naringenin, hesperidin, magnolol and honokiol; 160-0.63 ng/mL for rheochrysidin. The lower limit of quantification was: 19.53 ng/mL for rhein; 3.13 ng/mL for emodin, aloe-emodin, chrysophanol, naringin, naringenin, hesperidin, magnolol and honokiol; 0.6 3 ng/mL for rheochrysidin. The overall mean accuracy for the 10 major components of Da-Cheng-Qi decoction was 90.40-108.60%. Intra-day and inter-day precision was < or =12.43% and < or =11.32%, respectively. We conclude that this method is appropriate for simultaneous determination of the 10 major components of Da-Cheng-Qi decoction in dog plasma and the investigation of the pharmacokinetics of Da-Cheng-Qi decoction in dog.

Objective: To develop a sensitive LC-MS/MS method for analyzing lovastatin and its active metabolites lovastatin acid in human plasma., Methods: Lovastatin and lovastatin acid were extracted from plasma by ethyl ether -dichloromethane (V/V, 1:1), with simvastatin serving as an internal standard. The analytes went through the column of Phenomenex Gemini C18 (50 x 3 mm, 3 microm) with mobile phase acetonitrile-water (85:15), and was analyzed by API3000 after protonated with ESI mode. The ion pairs being detected were 427.4-->325.4, 445.4-->343.4 and 436.4-->325.4, respectively., Results: The established method was able to determine lovastatin in human plasma over the range of 0.03125-64 microg/L, with recovery rates ranging from 96% to 102%. The intra and inter day variances were below 9.3%., Conclusion: The LC-MS/MS method for analyzing lovastatin is validated and is suitable for clinical pharmacokinetic studies.