A bibliometric and thematic analysis of the trends in the research on ginkgo biloba extract from 1985 to 2022.

Background: Ginkgo biloba extract (GBE), a complementary and alternative medicine, has been widely used for disorders such as brain infarction, dementia, and coronary heart disease, in recent decades. Given its widespread clinical use, GBE has always been a vital research topic. However, there are no bibliometric analyses on this topic; furthermore, published reviews of GBE focus only on a specific research field or lack scientific and systematic evaluation. This study combined bibliometrics with thematic reviews by visual analysis to identify the current status of GBE research and to better identify research hotspots and trends in the past 40 years to understand future developments in basic and clinical research. Methods: Articles and reviews on GBE were retrieved by topic from the Web of Science Core Collection from inception to 2022.12.01. Countries, institutions, authors, journals, references, and keywords in the field were visually analyzed using CiteSpace, Scimago Graphica, and VOSviewer software; then, these visualization results for references and keywords were clarified in detail by thematic reviews in subdivisions of the fields. Results: In total, 2015 publications were included. The GBE-related literature has high volumes of publications and citations. The majority of literature is from China, and the USA cooperates most closely with other countries. In GBE research, Christen Yves is the most cited author, Phytotherapy Research is the most prolific journal, and the Journal of Ethnopharmacology is the most co-cited journal. Through a comprehensive analysis of keywords, references, and reviews, the quality of the meta-analysis of randomized controlled clinical trials of GBE in treating dementia was evaluated by the Risk of Bias in Systematic Reviews scale (ROBIS). Current research on GBE focuses on its pharmacological mechanisms, and neuroprotective application in diseases such as Alzheimer's disease, and glaucoma. Randomized controlled trials are the current research hotspot. Conclusion: Research on GBE is flourishing; using bibliometric and thematic analysis, we identified its hotspots and trends. The pharmacological mechanisms and clinical applications of GBE are the focus of present and likely future research.

Early efficacy of postoperative rehabilitation training for lumbar disc herniation.

OBJECTIVE: To investigate the early clinical efficacy of rehabilitation training after unilateral biportal endoscopy for lumbar disc herniation and to analyze the prognostic factors. METHODS: A total of 100 patients with lumbar disc herniation who underwent unilateral biportal endoscopy at The Sixth Affiliated Hospital of Nantong University from January 2019 to January 2021 were retrospectively analyzed. The control group was given a standard home-based exercise program, while the intervention group was given a substituted rehabilitation training opposed to a standard home-based exercise program. The early postoperative pain relief and quality of life values were compared between the two groups, and the independent risk factors affecting the prognosis of patients were analyzed. RESULTS: There were no significant differences in sex, age, smoking, drinking, BMI, course of disease, type of disc herniation, preoperative VAS, ODI or SF-36 between the two groups (P > 0.05). There was no significant difference in preoperative and postoperative VAS and ODI scores at 3 months between the two groups (P > 0.05), yet there were significant differences in postoperative VAS and ODI at 12 months (P < 0.05). The SF-36 score of the intervention group was lower than that of the control group at 12 months, and the difference was statistically significant (P < 0.05). The excellent rate of the Macnab standard modification used in the intervention group was 88.00% at 12 months, and that in the control group was 62.00%. The difference between the two groups was considered to indicate a statistically significant (P < 0.05). The results of logistic multivariate regression model analysis showed that rehabilitation training (95% CI: 1.360-12.122, P = 0.012), the type of intervertebral disc (95% CI: 0.010-0.676, P = 0.020), and age (95% CI: 1.056-8.244, P = 0.039) were independent risk factors affecting the prognosis of patients. CONCLUSION: Postoperative rehabilitation training can effectively relieve pain and improve quality of life; thus, it is highly recommended in the clinic. Postoperative rehabilitation training, intervertebral disc type and age are independent risk factors for the postoperative prognosis of lumbar intervertebral disc herniation.

Rapid simultaneous determination of thirteen aristolochic acids analogs in Aristolochiaceae plants by Ultra-High-Performance liquid Chromatography- tandem mass spectrometry in dynamic multiple reaction monitoring mode.

Asarum and Aristolochia are two large genera of Aristolochiaceae plants containing typical toxicant aristolochic acid analogs(AAAs), AAAs can be deemed as toxicity markers of Aristolochiaceae plants. Based on the least AAAs in dry roots and rhizomes of Asarum heterotropoides, Asarum sieboldii Miq and Asarum sieboldii var, all of which are enrolled in the Chinese pharmacopeia up to now. AAAs distribution in Aristolochiaceae plants, especially Asarum L. plants, is still obscure and controversial due to few AAAs measured, unverified species of Asarum, and complicated pretreatment in analytical samples making the results more challenging to reproduce. In the present study, a simple ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method in dynamic multiple reaction monitoring mode for simultaneous determination of thirteen AAAs was developed for evaluating the distribution of toxicity phytochemicals in Aristolochiaceae plants. The sample was prepared by extracting Asarum and Aristolochia powder with methanol, and the supernatant was analyzed using the Agilent 6410 system on an ACQUITY UPLC HSS PFP column with gradient elution of water and acetonitrile, containing 1% v/v formic acid (FA) each, at a flow rate of 0.3 mL/min. The chromatographic condition provided good peak shape and resolution. The method was linear over the specific ranges with the coefficient of determination (R2) > 0.990. Satisfactory intra- and inter-day precisions were achieved with RSD less than 9.79%, and the average recovery factors obtained were in the range of 88.50%～105.49%%. The proposed method was successfully applied for simultaneous quantification of the 13 AAAs in 19 samples from 5 Aristolochiaceae species, especially three Asarum L. species enrolled in the Chinese Pharmacopoeia. Except Asarum heterotropoides, the results supported that the Chinese Pharmacopoeia (2020 Edition) adopting the root with rhizome as medicinal parts of Herba Asari instead of the whole herb for drug safety by providing scientific data.

Aristolochic acid nephropathy: A scientometric analysis of literature published from 1971 to 2019.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy that may result in acute kidney injury and is associated with a potentially progressive course of kidney fibrosis and upper tract urothelial carcinoma. Aristolochic acids (AAs) are a group of toxins commonly present in plants of the genera Aristolochia and Asarum, which are found worldwide. AAN still occurs in Asian and Balkan regions. The progressive lesions and mutational events initiated by AAs are irreversible, and no effective therapeutic regimen for AAN has been established. Furthermore, more people are at risk of this disease due to casual exposure to AAs. This study performed a scientometric analysis of global research literature focusing on AAN. METHODS: The Web of Science database was searched to identify all publications pertaining to "aristolochic acid nephropathy" or "Balkan endemic nephropathy" using these terms as key words to search the literature from 1971 to 2019. The collected data included the document type, author, journal, publication year, citation reports, and country of publication, and were analyzed using the VOSviewer software. RESULTS: A total of 1251 records were initially obtained. Publication types, including "meeting abstract," "letter," "editorial material," and "proceedings paper" were excluded, which left 1083 publications comprising 923 articles and 160 reviews. English was the predominant language of the publications. China had the most number of articles published with 217 (20.0%), followed by the USA with 186 articles (17.2%), and Germany with 138 articles (12.7%). Kidney International, Food and Chemical Toxicology, and Toxins were the 3 most active journals in publishing articles related to AAN. The total number of citations received by all publications was 39,970, with an average of 36.91 citations per article (range: 0-1769). The literature mainly focused on apoptosis, oxidative stress, and inflammation in AAN. CONCLUSION: This study indicated that AAN is a significant topic in nephrology research, as shown by the large number of publications. The literature has mainly focused on the mechanisms of AA-induced nephropathy.

Study on the inhibition of inflammation by the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway and the promotion of wound healing of oral ulcer of Yangyin Shengji powder after chemotherapy.

BACKGROUND: To investigate the treatment effect and mechanism of Yangyin Shengji powder in oral ulcer after chemotherapy. METHODS: The experiments were externally administered. The threshold of pain reflex (Tr) was measured 30, 60, and 120 min after the last relative substances administration to the plantar and abdomen of mice by intelligent hot plate instrument. The toe swelling degree of mice was calculated 1, 3, and 5 h after inflammation. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and prostaglandin E2 (PGE2) were determined by enzyme-linked immunosorbent assay (ELISA), and the relative expression levels of cyclooxygenase-1 (COX-1) and COX-2 were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Two hours after the last spraying treatment, the ulcer area of mice was measured. Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR) were detected by ELISA. The degree of oral mucosal injury was observed by hematoxylin and eosin (HE) staining. RESULTS: Compared with positive control group, the Tr value of Yangyin Shengji powder group was lower at 30 and 60 min, and the Tr value was higher at 120 min. Yangyin Shengji powder decreased the swelling degree of toes 1, 3, and 5 h after inflammation, and the SOD and GSH-Px levels in the swelling tissue of toes were significantly increased. The MDA, PGE2, COX-1 and COX-2 levels were significantly decreased. The oral mucosa structure of mice in the Yangyin Shengji powder group was relatively intact and a few inflammatory cells were infiltrated. Compared with normal group, the levels of TNF-α and IL-6 in the model group were increased, while the levels of EGF and EGFR were decreased (P<0.01). Compared with the model group, ulcer area, TNF-α, and IL-6 levels were decreased in the Yangyin Shengji powder group, while EGF and EGFR levels were increased (P<0.01). CONCLUSIONS: Yangyin Shengji powder has anti-inflammatory and analgesic effects, is anti-oxidative stress, inhibits inflammatory response, and inhibits the COX-2/PGE2 signaling pathway, so as to alleviate local inflammation of oral ulcer in mice after chemotherapy and promote wound healing.

Structurally diverse diterpenoid alkaloids from the lateral roots of Aconitum carmichaelii Debx. and their anti-tumor activities based on in vitro systematic evaluation and network pharmacology analysis.

Thirty-seven diterpenoid alkaloids (DAs) with diverse structures were isolated and identified from the lateral roots of Aconitum carmichaelii Debx., comprising eight C20-DAs and twenty-nine C19-DAs. Besides the 31 known DAs identified by comparing the 1H NMR and 13C NMR data with those reported in the literature, the structures of four new compounds (1, 14, 17, and 25), and two other compounds (26 and 37) which were reported to be synthesized previously, were also elucidated based on the comprehensive analysis of their HR-ESI-MS, 1D and 2D NMR spectra, including 1H-1H COSY, HSQC and HMBC and NOESY/ROESY. Among them, compound 1 represents the first example of a C20-DA glucoside. Besides, the anti-tumor activities of all the isolated compounds against human non-small-cell lung cancer A549 and H460 cells were systematically evaluated by MTT methods. The results revealed that all of the C19-DAs possessed moderate activities against both of the two cell lines with IC50 values ranging from 7.97 to 28.42 µM, and their structure-activity relationships indicated the active sites of C-8, C-10, and C-14 positions and the nitrogen atom in the C19-DA skeleton. In addition, all of the isolated DAs, with chemical structures confirmed, were further applied for network pharmacology analysis, in order to give an insight into the possible mechanisms of their anti-tumor activities. As a result, 173 potential targets and three most important pathways related to non-small-cell lung carcinoma were finally unearthed.

Two New Aristolochic Acid Analogues from the Roots of Aristolochia contorta with Significant Cytotoxic Activity.

Twelve compounds, including two new aristolochic acid analogues with a formyloxy moiety (9-10) and 10 known aristolochic acid derivates (1-8 and 11-12), were obtained from the roots of Aristolochiacontorta. Their structures were elucidated using extensive spectroscopic methods. Their cytotoxic activity in human proximal tubular cells HK-2 was evaluated by the MTT method, which has been widely used to assess cell viability. Among these molecules, compounds 3 and 9 were found to be more cytotoxic. Furthermore, molecular modeling was used to evaluate, for the first time, the interactions of compounds 3 and 9 with the target protein organic anionic transporter 1 (OAT1) that plays a key role in mediating aristolochic acid nephropathy. Structure-activity relationships are briefly discussed.

Comparative Pharmacokinetic Profiles of Puerarin in Rat Plasma by UHPLC-MS/MS after Oral Administration of Pueraria lobata Extract and Pure Puerarin.

Puerarin is the main biologically active isoflavone in Pueraria lobata and has a wide range of biological activities. However, due to its poor water solubility and low oral bioavailability, its clinical applications are restricted. Compared with puerarin, the Pueraria lobata extract (PLE) has better water solubility, lower toxicity, and less side effects. In this study, the pharmacokinetics of orally administered puerarin (100 mg/kg) and PLE (763 mg/kg, equivalent to 100.0 mg/kg of puerarin) to rats was investigated by the UHPLC-MS/MS method. Results showed that when the rats were administered PLE, the area under the concentration-time curve from zero to infinity (AUC 0-inf ) dramatically increased from 219.83 ± 64.37 µg h/L to 462.62 ± 51.74 µg h/L (p < 0.01). The elimination half-time (t 1/2 ) also increased from 1.60 ± 0.38 h to 12.04 ± 5.10 h (p < 0.01). The maximum concentration (C max) of puerarin decreased from 101.64 ± 41.82 ng/mL to 48.64 ± 21.47 ng/mL (p < 0.01), and time to reach the maximum plasma concentration (T max) of puerarin decreased from 1.46 ± 1.08 h to 0.54 ± 0.30 h (p < 0.01). Results indicated that the pharmacokinetics of puerarin in Pueraria lobata may be dramatically different from pure puerarin in the plasma of rat, and oral bioavailability of puerarin may be increased when PLE was administrated to rats.

Ginkgol Biloba extract as an adjunctive treatment for ischemic stroke: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: Ginkgo biloba extract (GBE) is widely used as an adjunctive treatment for ischemic stroke. This meta-analysis aimed to evaluate the effectiveness and safety of GBE specifically for long-term users at the convalescence stage of ischemic stroke. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials, Embase Database, WHO Clinical Trials Registration Platform, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from inception to 20 September 2018. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were used as effect estimates using RevMan software (5.3; Review Manager [RevMan], Nordic Cochrane Centre, Copenhagen, Denmark). A meta-analysis was performed where data were available. A trial sequential analysis was used to control random errors for recurrence rate and the GRADE (grading of recommendations, assessment, development, and evaluations) approach was used to assess the quality of the body of evidence. The meta-analysis design was registered on PROSPERO (CRD42018110211, http://www.crd.york.ac.uk/PROSPERO). RESULTS: We identified 15 randomized clinical trials involving 1829 participants. The majority of the included trials were of high risk of bias in methodological quality. For acute ischemic stroke, adding GBE to conventional therapy led to higher Barthel index scores (MD: 5.72; 95% CI: 3.11-8.33) and lower neurological function deficit scores (MD: -1.39; 95% CI: -2.15 to -0.62). For patients in their convalescence (or sequelae) stage of ischemic stroke, GBE was superior in improving dependence (MD: 7.17; 95% CI: 5.96-8.38) and neurological function deficit scores (MD: -1.15; 95% CI: -1.76 to -0.53) compared with placebo or conventional therapy, but there was no difference in vascular events (RR: 0.70; 95% CI: 0.44-1.14), recurrence rate (RR: 0.57; 95% CI: 0.26-1.25; trial sequential analysis: conclusive) and mortality (RR: 1.07; 95% CI: 0.41-2.81). CONCLUSIONS: GBE appears to improve neurological function and dependence compared with conventional therapy for ischemic stroke at different stages and appears generally safe for clinical application. The lack of improvement in recurrence rate was confirmed by trial sequential analysis. Due to the generally weak evidence, further large, rigorous trials are warranted.

Simultaneous determination of resibufogenin and its eight metabolites in rat plasma by LC-MS/MS for metabolic profiles and pharmacokinetic study.

BACKGROUND: Resibufogenin is one of the main active compounds of Venenum Bufonis and exhibits diverse pharmacological activities. It is brought into focus for its potency in heart failure and cancer therapy. PURPOSE: The purpose of this study was to establish a convenient and effective method which was used to simultaneously determine the resibufogenin and its metabolites in rat plasma for further understanding the metabolic profiles of resibufogenin in vivo and pharmacokinetic study by LC-MS/MS. METHODS: The analytes were separated on a BEH C18 column with a mobile phase of water containing 0.05% formic acid and acetonitrile under gradient elution at a flow rate of 0.4 ml/min. Resibufogenin and its eight metabolites were quantified in positive electrospray ionization and MRM mode with transitions of m/z 385.5→349.2 for resibufogenin; m/z 513.7→145.3 for IS (internal standard); m/z 401.23→365.21, m/z 417.23→285.21 and m/z 385.24→349.21 for three main metabolites (hydroxylated-resibufogenin; dihydroxylated-resibufogenin and 3-epi-resibufogenin, respectively). RESULTS: This method was successfully validated with a good linearity over the concentration ranges of 1-200 ng/ml for resibufogenin and the correlation coefficients was more than 0.990. The lower limit of quantification was 1 ng/ml and the precision and accuracy values were less than 15%. The method was applied to study the metabolic profiles of resibufogenin in rat plasma after oral administration of 20 mg/kg. The results indicated that the metabolic reactions of resibufogenin were mainly hydroxylation, dihydroxylation, dehydrogenation and isomerization. Totally eleven metabolites were identified, among which eight were successfully quantified. CONCLUSION: The results could provide further research foundation for the mechanisms study of activity and toxicity in vivo and facilitate the appropriate clinical application of resibufogenin.

Simultaneous Determination of Bufalin and Its Nine Metabolites in Rat Plasma for Characterization of Metabolic Profiles and Pharmacokinetic Study by LC⁻MS/MS.

Characterization and determination of metabolites to monitor metabolic pathways play a paramount role in evaluating the efficacy and safety of medicines. However, the separation and quantification of metabolites are rather difficult due to their limited contents in vivo, especially in the case of Chinese medicine, due to its complexity. In this study, an effective and convenient method was developed to simultaneously quantify bufalin and its nine metabolites (semi-quantitation) in rat plasma after an oral administration of 10 mg/kg to rats. The prototype and metabolites that were identified were subsequently quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 387.4→369.6 and 387.4→351.3 for bufalin, m/z 513.7→145.3 for IS, and 387.4→369.6, 419.2→365.2, and 403.2→349.2 for the main metabolites (3-epi-bufalin, dihydroxylated bufalin, and hydroxylated bufalin, respectively). The method was validated over the calibration curve range of 1.00-100 ng/mL with a limit of quantitation (LOQ) of 1 ng/mL for bufalin. No obvious matrix effect was observed, and the intra- and inter-day precisions, as well as accuracy, were all within the acceptable criteria in this method. Then, this method was successfully applied in metabolic profiling and a pharmacokinetic study of bufalin after an oral administration of 10 mg/kg to rats. The method of simultaneous determination of bufalin and its nine metabolites in rat plasma could be useful for pharmacokinetic-pharmacodynamic relationship research of bufalin, providing experimental evidence for explaining the occurrence of some adverse effects of Venenum Bufonis and its related preparations.

Four New Depsides Isolated from Salvia miltiorrhiza and Their Significant Nerve-Protective Activities.

By investigating of the roots of Salvia miltiorrhiza, which is one of the most widely used Chinese herbs, we used phytochemical methods successfully to obtain twelve depsides: four depsides (1⁻4) that were previously undescribed, along with eight known ones (5⁻12). Their structure characteristics were assessed by HR-ESIMS, CD, NMR (¹H, 13C, HSQC, HMBC) data analyses. These four newly isolated compounds (1⁻4), as well as the other eight compounds (5⁻12), show extraordinary protective effects on hydrogen peroxide-induced apoptosis in HS-SY5Y cells. Among them, depside 4 and depside 6 displayed more obviously protective effects than others.

A rare case of methimazole-induced cholestatic jaundice in an elderly man of Asian ethnicity with hyperthyroidism: A case report.

BACKGROUND: Methimazole is an antithyroid drug that is widely used for the treatment of hyperthyroidism. As an inhibitor of the enzyme thyroperoxidase, methimazole is generally well-tolerated. However, there have been increasing reports of methimazole-induced liver damage, although this effect of methimazole has been limited by the absence of objective diagnosis of the liver condition or the inappropriate use of the Naranjo scale. We present the case of an elderly man with hyperthyroidism, gastritis, and epilepsy who developed liver damage after administration of multiple drugs. KEY POINTS FROM THE CASE: Considering the low sensitivity of the Naranjo scale in detecting rare reactions associated with liver damage, we used the Roussel-Uclaf Causality Assessment Method scale, with a finding of cholestatic jaundice hepatitis induced by methimazole. The patient's liver enzyme levels improved after discontinuation of methimazole. MAIN LESSONS LEARNED: Our case underlines the possible hepatoxicity associated with the use of methimazole. A review of the literature confirmed a selective hepatoxicity risk in individuals of Asian ethnicity, which has not been identified in Caucasian or Black populations. Physicians should be aware of the risk of hepatoxicity when prescribing oral methimazole to patients of Asian ethnicity.

Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study.

BACKGROUND: Meclofenoxate hydrochloride is a psychostimulant in the nootropic agent group available in capsule and tablet formulations approved for traumatic cataphora, alcoholic poisoning, anoxia neonatorum, and children's enuresis in China. Although these 2 generic formulations are marketed in China, information regarding their pharmacokinetics and bioequivalence in humans has not been published. OBJECTIVE: The aim of this study was to compare the pharmacokinetic properties and bioequivalence of the capsule (test) and tablet (reference) formulations of meclofenoxate hydrochloride 200 mg in healthy Chinese volunteers. METHODS: This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University, Nanjing, China. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 200-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. As a prodrug, meclofenoxate is hydrolyzed into 4-chlorophenoxyacetic acid and is not detected in plasma. The active metabolite of meclofenoxate, chlorophenoxyacetic acid, was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including Cmax, AUC0-24, and AUC0-infinity, blood samples were obtained at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 14, and 24 hours after administration. The formulations were considered bioequivalent if the log-transformed ratios of Cmax and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Subjects were interviewed concerning the occurrence of adverse events including excitement, insomnia, lassitude, and headache. Tolerability was assessed at baseline (before administration) and at 1, 2, 6, and 12 hours after administration by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis). RESULTS: Twenty-four Chinese male subjects (mean [range]age,23.5[22-30]years;weight,63.3[56-68]kg; height, 171 [165-184] cm) were enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of chlorophenoxyacetic acid Cmax, AUC0-24, and AUC0-infinity were 95.7 to 122.9, 97.6 to 111.9, and 97.8 to 111.7, respectively (all, P>0.05). Similar results were found for the data without log-transformation. No adverse events were reported or observed during this single-dose study. CONCLUSIONS: In this small study in healthy Chinese adult male volunteers, a single 200-mg dose of the capsule formulation was found to be bioequivalent to a single 200-mg dose of the tablet formulation based on the US FDA's regulatory definition (rate and extent of absorption). Both formulations were well tolerated.

Determination of azelnidipine by LC-ESI-MS and its application to a pharmacokinetic study in healthy Chinese volunteers.

A simple, rapid and sensitive high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) assay for determination of azelnidipine in human plasma using perospirone as the internal standard (IS) was established. After adjustment to a basic pH with sodium hydroxide solution, plasma samples were extracted with diethyl ether and separated on a C18 column with a mobile phase of methanol-5 mM ammonium acetate solution (90:10, v/v). The lower limit of quantification (LLOQ) was 0.20 ng/ml. After administration of a single dose of azelnidipine 8mg and 16 mg, respectively; the area under the plasma concentration versus time curve from time 0 h to 96 h (AUC(0-96) were (186 +/- 47) ng ml(-1) h, (429 +/- 145) ng ml(-1) h, respectively; clearance rate (CL/F) were (45.94 +/- 11.61), (42.11 +/- 14.23) L/h, respectively; peak plasma concentration Cmax were (8.66 +/- 1.15), (19.17 +/- 4.13) ng/ml, respectively; apparent volume of distribution (Vd) were (1749 +/- 964), (2480 +/- 2212) L, respectively; time to Cmax (Tmax) were (2.8 +/- 1.2), (3.0 +/- 0.9) h, respectively; elimination half-life (t(1/2beta)) were (22.8 +/- 2.4), (23.5 +/- 4.2) h, respectively; and MRT were (25.7 +/- 1.3), (26.2 +/- 2.2) h, respectively; The essential pharmacokinetic parameters after oral multiple doses (8 mg, q.d.) were as follows: (Cmax) ss, (15.04 +/- 2.27) ng/ml; (Tmax) ss, (2.38 +/- 0.92) h; (Cmin) ss, (3.83 +/- 0.94) ng/ml; C(av), (7.05 +/- 1.54) ng/ml; DF, (1.62 +/- 0.26); AUCss, (169.19 +/- 36.87) ng ml(-1) h.