Comparative pharmacokinetics of nine major bioactive components in normal and ulcerative colitis rats after oral administration of Lizhong decoction extracts by UPLC–TQ–MS/MS

Lizhong decoction (LZD), a classic formula, has been used to treat ulcerative colitis (UC) for thousands of years in clinical practice. However, the pharmacokinetic characteristics of its major bioactive components in rats under different physiological and pathological states are not clear. Thus, in this study, a rapid and sensitive analytical method, ultra‐performance liquid chromatography coupled with mass spectrometry (UPLC–MS/MS) method, was developed and applied to simultaneously determine glycyrrhizic acid, liquiritin, isoliquiritin, glycyrrhizin, isoliquiritigenin, 6‐gingerol, ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Re in normal and UC rats after oral administration of LZD extract. A Waters BEH C₁₈ UPLC column was used for chromatographic separation, while acetonitrile and 0.1% formic acid were selected as mobile phase. The linearity of nine analytes was >0.9920. Inter‐ and intra‐day accuracy was ≤ 11.4% and precision was from 1.1 to 12.7%. Additionally, stable and suitable extraction recoveries were also obtained. The established method was validated and found to be specific, accurate and precise for nine analytes. Furthermore, it was successfully applied to the pharmacokinetic investigation of nine major components after oral administration of LZD extracts to normal and model rats, respectively. The results showed that the pharmacokinetic parameters (C_max, T_max, AUC_0–t, AUC_0–∞) in the plasma of UC rats were significantly different from those of normal rats, which could provide a reference for the clinical application of LZD.     

Comparative pharmacokinetics of prim-O-glucosylcimifugin and cimifugin by liquid chromatography-mass spectrometry after oral administration of Radix Saposhnikoviae extract, cimifugin monomer solution and prim-O-glucosylcimifugin monomer solution to rats

A sensitive and reliable liquid chromatography–mass spectrometry method has been developed and validated for simultaneous determination of cimifugin and prim‐O‐glucosylcimifugin in rat plasma after oral administration of Radix Saposhnikoviae (RS) extract, prim‐O‐glucosylcimifugin monomer solution and cimifugin monomer solution. Plasma samples were pretreated by protein precipitation with acetonitrile containing the internal standards puerarin and daidzein. LC separation was achieved on a Zorbax SB‐C₁₈ column (150 × 4.6 mm i.d., 5 µm) with 0.1% formic acid in water and methanol by isocratic elution. The detection was carried out in select‐ion‐monitoring mode with a positive electrospray ionization interface. The fully validated method was successfully applied to the pharmacokinetic study of the analytes in rats. A bimodal phenomenon appeared in the concentration–time curve of prim‐O‐glucosylcimifugin and cimifugin after oral administration of RS extract. Prim‐O‐glucosylcimifugin mainly transformed to cimifugin when it was absorbed into blood. Both absorption and elimination of cimifugin after oral administration of RS were longer than after administration of single cimifugin. The pharmacokinetic parameters (AUC_0–t, AUC_0–∞ and t_1/2) of prim‐O‐glucosylcimifugin and cimifugin by giving cimifugin monomer solution, prim‐O‐glucosylcimifugin monomer solution and RS extract had significant differences (P < 0.05). Copyright © 2012 John Wiley & Sons, Ltd.     

Simultaneous quantification of ligustilide,dl‐3‐n‐butylphthalide and senkyunolide A in rat plasma by GC–MS and its application to comparative pharmacokinetic studies of Rhizoma Chuanxiong extract alone and Baizhi Chuanxiong Decoction

The herb couple has special clinical significance in reducing the toxicity and increasing the efficacy of drugs. The combination of Radix Angelicae Dahuricae (Baizhi, BZ) and Rhizoma Chuanxiong (ChuanXiong, CX) is a traditional herb couple. The combination performs better than the CX extract alone in the treatment of migraine and has been used for thousands of years. However, the specific compatibility mechanisms are still unclear. Ligustilide, dl ‐3‐n‐butylphthalide and senkyunolide A are the major active ingredients in CX and BZ–CX decoction. However, a comprehensive study of the pharmacokinetics of CX has not been carried out. A gas chromatography–mass spectroscopy (GC–MS) method with high selectivity, sensitivity and accuracy was developed. An SH‐Rxi‐5Sil (30 m × 0.25 mm i.d., and 0.25 μm film thickness) column was employed in the GC separation. Selectivity, linearity, precision, accuracy, recovery, matrix effect and stability were used to validate the current GC–MS method. Using the validated method, this is the first time to study on the comparative pharmacokinetics of ligustilide, dl ‐3‐n‐butylphthalide and senkyunolide A from CX alone and BZ–CX decoction in rat plasma. The pharmacokinetic parameters (C_max, T_max, T_1/2, AUC_0–t, AUC_0–∞ and CLz/F) of all of the detected ingredients showed significant differences between the two groups (P < 0.05). The results are helpful for further investigation of the compatibility mechanism of BZ–CX decoction.     

Comparative pharmacokinetics of three monoester‐diterpenoid alkaloids after oral administration of Acontium carmichaeli extract and its compatibility with other herbal medicines in Sini Decoction to rats

Sini decoction (SND) is an important traditional Chinese multiherbal formula, which is widely used to treat cardiovascular disease. Acontium carmichaeli (AC) is a leading herb in SND, whose main components are monoester‐diterpenoid alkaloids (MDAs). The aim of this study is to compare the pharmacokinetics of three MDAs in rat plasma after oral administration of AC extract and its compatibility with other herbal medicines in SND. A sensitive, accurate and specific LC‐MS/MS method was developed to determine the contents of three MDAs in rat plasma. Male Sprague–Dawley rats were randomly assigned to four groups: AC, AC + ZO, AC + GU and SND groups. There were significant differences in the pharmacokinetic parameters (C_max, T_max, t_1/2, AUC_(0–24), MRT and CL). Compared with the AC group, C_max, AUC_(0–24) and CL of three MDAs increased and t_1/2 decreased in AC + ZO, AC + GU and SND groups. Little changed in the AC + GU group in comparison with AC + ZO group, which indicated that other ingredients in ZO may promote the absorption rate and accelerate excretion rate of MDAs. The results could be helpful for revealing the compatibility mechanism of Chinese multiherbal medicine and providing clinical medication guidance on AC and its compatibility with other herbal medicines in SND. Copyright © 2014 John Wiley & Sons, Ltd.     

Evaluation of the influence of mirabilite on the absorption and pharmacokinetics of the ingredients in Dahuang‐mudan decoction by a validated UPLC/QTOF–MS/MS method

Dahuang‐mudan decoction (DMD) has been widely used for disease treatment in China for 1700 years. The formula consists of Rhubarb, moutan bark, Prunus persica, wax gourd kernel and mirabilite, which have been well studied by multidisciplinary approaches. However, the role of the mineral mirabilite in DMD is unclear. The objective of this study was to investigate the effects of mirabilite on the absorption and pharmacokinetics of the ingredients in DMD. The constituents were identified in DMD extract and the plasma of mirabilite–DMD (MDMD, 50 g kg^?1) treated rats and nonmirabilite–DMD (NMDMD, 50 g kg^?1) treated rats. The plasma was also used to investigate the effects of mirabilite on the pharmacokinetics of active ingredients in DMD using a new validated UPLC–MS/MS method. The results showed that 63 compounds were identified in the extract of DMD, 27 and 22 of which were found in the plasmas of MDMD‐ and NMDMD‐treated rats, respectively. Furthermore, the results of a pharmacokinetic study suggested that mirabilite influenced the absorption of the five constituents by decreasing the absorption of emodin and rhein while increasing the absorption of aloe‐emodin, paeoniflorin and amygdalin; the pharmacokinetic parameters, including the T_max, C_max, AUC_0–t, MRT_0–t, CLz and t_1/2 of five constituents, significantly changed in MDMD‐treated rats compared with the NMDMD. The method validation for selectivity, precision, accuracy, matrix effect, recovery and stability met the acceptance criteria. These findings uncover the roles of mirabilite in DMD and demonstrate the application of scientific principles to the study of DMD in human health care.     

Micellar liquid chromatographic method for the determination of ephedrine and pseudoephedrine in human serum by direct inject of the sample with simple dilution

A micellar high-performance liquid chromatographic method was developed to simultaneously determine ephedrine and pseudoephedrine in human serum. The serum sample pretreatment was a simple dilution in a micellar solution, filtration, and direct injection, thus avoiding time-consuming and tedious steps. Hence, there is no need to use an internal standard. The serum samples were analyzed using a mobile phase containing 1.50?×?10^?1?mol/L sodium dodecyl sulfate and 0.02?mol/L sodium dihydrogen phosphate with 7.5% (v/v) 1-propanol at pH 3.0, running at 1.0?mL/min by an Inertsil C18 (150?×?4.6?mm, 5?µm) column at 30°C. The UV wavelength was set at 210?nm. The developed method was validated by linearity (r?>?0.9990) and intra- and inter-day precisions of ephedrine and pseudoephedrine (relative standard deviation; RSD%, 0.04–10.40, and RSD %, 0.30–10.25, respectively), LODs for ephedrine and for pseudoephedrine was 2.63 and 2.70?µg/mL, respectively; lower limit of quantification for ephedrine and for pseudoephedrine was 4.38 and 4.51?µg/mL, respectively. Finally, the proposed method was applied to investigate ephedrine and pseudoephedrine in real human serum samples after oral administration of Kechuanning Koufye including Ephedra herb. It is environmentally friendly, easy-to-handle, and feasible method for routine analysis in clinical laboratory.     

Comparative pharmacokinetic study of the main components of cortex fraxini after oral administration in normal and hyperuricemic rats

Cortex Fraxini is an important traditional Chinese herbal medicine used for the treatment of gout and hyperuricemia. An efficient and rapid ultra‐performance liquid chromatography mass spectrometry method was developed and validated for simultaneous quantitation of six coumarins (aesculin, fraxin, aesculetin, fraxetin, sopoletin and 7‐hydroxycoumarin) in normal and hyperuricemic rats plasma after oral administration of Cortex Fraxini. The method could successfully be applied for pharmacokinetics studies. The pharmacokinetic behavior of six coumarins in normal and hyperuricemia rats plasma was determined. Results showed that, for some of analytes, the pharmacokinetic parameters (AUC_0–t , AUC_0–∞, C _max, T _max and CL ) were significantly different between normal and hyperuricemic rats. The different pharmacokinetic parameters might result from renal impairment or a change of metabolic enzymes in the pathological state. The pharmacokinetic study in pathological state could provide more useful information to guide the clinical use of traditional Chinese herbal medicine.     

Comparative pharmacokinetics studies of benzoylhypaconine,benzoylmesaconine, benzoylaconine and hypaconitine in rats by LC‐MS method after administration of Radix Aconiti Lateralis Praeparata extract and Dahuang Fuzi Decoction

A rapid and sensitive high‐performance liquid chromatography–mass spectrometric (HPLC‐MS) method was developed and validated for simultaneous determination of benzoylhypaconine (BHA), benzoylmesaconine (BMA), benzoylaconine (BAC) and hypaconitine (HA) in rat plasma for the first time. The analytes were separated on a Kromasil C₁₈ column with a total running time of 11 min. The validation data demonstrated a sound feasibility for the newly developed method and it was then applied to the pharmacokinetic study of these analytes in rats. Pharmacokinetic behaviors of BHA, BMA, BAC and HA in rats were studied after oral administration of Radix Aconiti Lateralis Praeparata extract (FZ) and Dahuang Fuzi Decoction (DFD). The main parameters for the two groups of subjects were compared, and significant differences between Radix Aconiti Lateralis Praeparata extract group and Dahuang Fuzi Decoction group in calculated parameters, such as the area under the plasma concentration–time from zero to the last quantifiable time‐point (AUC_0–t), the area under the plasma concentration–time curve from zero to infinity (AUC_0–∞), peak plasma concentration (C_max), half‐life of elimination (T_1/2), mean retention time (MRT_0–t), plasma clearance (CL), volume of distribution (V_d) and time to reach C_max (T_max), were found. After oral administration of DFD, the AUC_0–t, AUC_0–∞ and C_max of BHA, BMA, BAC and HA decreased remarkably (p < 0.05) compared with those of the FZ extract group. V_d and CL values of BHA, BMA, BAC and HA increased, two of which showed significant difference (p < 0.05). T_1/2 and MRT_0–t values of BHA, BMA and BAC in the DFD group were significantly delayed compared with those of FZ extract group. Only the T_max of HA, the toxic ingredient in FZ, delayed significantly in DFD group compared with the value of FZ group. All these pharmacokinetic parameters were statistically compared, and the rationality of the combination for DFD was clearly demonstrated. Copyright © 2013 John Wiley & Sons, Ltd.     

Formation of Diastereoisomerically Pure Oxazaphospholes and Their Reaction to Chiral Phosphane‐Borane Adducts

Starting with achiral phosphines and (1S,2S)‐2‐(methylamino)‐1‐phenylpropan‐1‐ol ((+)‐pseudoephedrine) or (1R,2S)‐2‐(methylamino)‐1‐phenylpropan‐1‐ol ((−)‐ephedrine), as chiral auxiliaries, diastereoisomerically pure oxazaphospholes were prepared (Scheme 1). The configuration at the P‐atom is controlled by the configuration at the Ph‐substituted C(1) of (+)‐pseudoephedrine or (−)‐ephedrine, respectively. This was confirmed by X‐ray crystal‐structure analyses of two intermediate compounds in the synthesis route to the chiral triarylborane‐phosphane adducts.     

Simple HPLC method for detection of trace ephedrine and pseudoephedrine in high-purity methamphetamine

A simple and sensitive HPLC technique was developed for the qualitative determination of ephedrine and pseudoephedrine (ephedrines), used as precursors of clandestine d‐methamphetamine hydrochloride of high purity. Good separation of ephedrines from bulk d‐methamphetamine was achieved, without any extraction or derivatization procedure on a CAPCELLPACK C₁₈ MGII (250 × 4.6 mm) column. The mobile phase consisted of 50 mM KH₂PO₄–acetonitrile (94:6 v/v %) using an isocratic pump system within 20 min for detecting two analytes. One run took about 50 min as it was necessary to wash out overloaded methamphetamine for column conditioning. The analytes were detected by UV absorbance measurement at 210 nm. A sample (20 mg) was simply dissolved in 1 mL of water, and a 50 μL aliquot of the solution was injected into the HPLC. The detection limits for ephedrine and pseudoephedrine in bulk d‐methamphetamine were as low as 3 ppm each. This analytical separation technique made it possible to detect ephedrine and/or pseudoephedrine in seven samples of high‐purity d‐methamphetamine hydrochloride seized in Japan. The presence of trace ephedrines in illicit methamphetamine may strongly indicate a synthetic route via ephedrine in methamphetamine profiling. This method is simple and sensitive, requiring only commonly available equipment, and should be useful for high‐purity methamphetamine profiling. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparative pharmacokinetic study of six lignans in normal and diabetic rats after oral administration of Saururus chinensis extract by LC–MS/MS

Saururus chinensis (SC) possesses significant anti-diabetic activity and lignans were its major bioactive compounds. In this study, a rapid and sensitive ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was established for simultaneous quantification of six lignans, namely (-)-(7R,8R)-machilin D ( 1 ), verrucesin ( 2 ), rel-(7S,8S,7′R,8′R)-3,3′,4,4′,5,5′-hexamethoxy-7.O.7′,8.8′-lignan ( 3 ), manassantin A ( 4 ), manassantin B ( 5 ), and saucerneol F ( 6 ) in rat’s plasma. It was validated with acceptable linearity (r ≥ 0.9922), accuracy (80.42–95.17%), precision (RSD ≤ 12.08%), and extraction recovery (80.36–93.45%). The method was successfully applied to the comparative pharmacokinetic study of the six lignans in normal and diabetic rats after oral administration of SC extract. Results showed that the areas under the plasma concentration-time curve (AUC_{0 → t} and AUC_{0 → ∞}) of (-)-(7R,8R)-machilin D, rel-(7S,8S,7′R,8′R)-3,3′,4,4′,5,5′-hexamethoxy-7.O.7′,8.8′-lignan, manassantin B, and saucerneol F in diabetic rats were significantly increased, and the plasma clearance (CL) of (-)-(7R,8R)-machilin D in diabetic rats was significantly decreased. However, the AUC_{0 → t} and AUC_{0 → ∞} of verrucesin were significantly decreased, and its CL was significantly increased in diabetic rats compared with those in normal rats. These results indicated that there were remarkable differences in the pharmacokinetic parameters between the normal and diabetic rats. The pharmacokinetic studies might be beneficial for the clinical use of SC as hypoglycemic agent.     

A sensitive UPLC–MS/MS method for simultaneous determination of polyphenols in rat plasma: Application to a pharmacokinetic study of dispensing granules and standard decoction of Cinnamomum cassia twigs

This study established a rapid and reliable approach using liquid chromatography–tandem mass spectrometry for the simultaneous determination of cinnamic acid, vanillic acid and protocatechuic acid in rat plasma. This is the first report on a comparative pharmacokinetic study of dispensing granules and standard decoction of Cinnamomum cassia twigs in rats. After liquid–liquid extraction by ethyl acetate, the plasma samples were subjected to LC–MS/MS for multiple reaction monitoring. The standard curves showed good linear regression (r² > 0.9991) in the range of 10.0–16000 ng/mL. The intra‐ and inter‐day accuracy and precision were found to be within 15% of the nominal concentration. The recoveries of the three phenolics ranged from 88.7 to 105.7%. Finally, this approach was successfully applied to pharmacokinetic analysis of the three phenolics after oral administration of standard decoction and dispensing granules of C. cassia twigs in rats. Although the values of AUC_0–t of vanillic acid and protocatechuic acid in standard decoction group were larger than those of the dispensing granule group, no significant difference was observed for the two groups. Of note, the elimination rates of vanillic acid were slower in the standard decoction group than the dispensing granule group.     

Comparative pharmacokinetics of the main active components in normal and ulcerative colitis rats after oral administration of Zingiberis Rhizoma–Ginseng Radix et Rhizoma herb pair and its single herb extracts by LC–MS/MS

Zingiberis Rhizoma and Ginseng Radix et Rhizoma are usually used together for the treatment of ulcerative colitis in clinical practices. However, their compatibility mechanism remains unclear. In this study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6-gingerol in rat plasma after oral administration of Zingiberis Rhizoma–Ginseng Radix et Rhizoma herb pair and its single herb extracts. The calibration curves exhibited good linearity, with correlation coefficients of more than 0.993. The precision deviations of intra- and interday analysis were within 10.66%, and accuracy error ranged from −12.74 to 11.56%. The average recoveries of analytes were higher than 76.60% and the matrix effects were minimal. Thus, the validated method was successfully applied to a pharmacokinetic study of four ingredients in normal and ulcerative colitis rat plasma. The results indicated that the pharmacokinetic parameters of four analytes in normal and model groups showed significant differences. The larger exposure (the mean AUC_0-t of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6-gingerol were increased by 50.93, 141.90, 3.68, and 37.25%, respectively) and slower elimination (the CLz/F of ginsenoside Re, ginsenoside Rg1, and 6-gingerol were decreased by 52.94, 83.64, and 32.18%, respectively) were observed in ulcerative colitis rats. Furthermore, compared with single herbs, the analytes in rat plasma after oral administration of combined extracts presented relatively high systemic exposure levels with AUC_0-t > 2000 h·ng/mL and C_max > 200 ng/mL. Collectively, the differences of pharmacokinetic characteristics revealed the synergistic effect of Zingiberis Rhizoma–Ginseng Radix et Rhizoma herb pair, which provided a valuable and reliable basis for its clinical application in the treatment of ulcerative colitis.     

Metabolic characteristics and pharmacokinetic differences of Qiwei Tongbi oral liquid in rheumatoid arthritis rats

Qiwei Tongbi oral liquid (QWTB), a classical traditional Chinese medicine formula, is widely used to treat arthritis-related diseases in clinical practice. Currently, in vivo metabolic characteristics and pharmacokinetic studies are lacking. This study analyzed the prototype components of QWTB absorbed in the blood and their metabolic transformation process after intragastric administration and compared the differences in pharmacokinetic properties between healthy and rheumatoid arthritis model rats. In sum, 17 prototype components and 21 related metabolites were identified in the plasma and urine of the treated rats. Metabolites were derived from sinomenine and magnoflorine. Through systematic methodology verification, an accurate and stable detection method for sinomenine and magnoflorine in plasma samples was established and applied to pharmacokinetic research of QWTB. At the three dose levels, the AUC_0–∞ (area under the curve) of the two components showed a good positive correlation with the dose (R² > 0.9). Compared with healthy rats, the T_max, t_1/2z, and AUC of sinomenine were markedly increased, and C_max was decreased in rheumatoid arthritis model rats, indicating that the rate of absorption and elimination rate decreased, but the body exposure increased. However, there were no significant differences in the pharmacokinetic parameters of magnoflorine under healthy and pathological conditions. In summary, the main active ingredients of QWTB are sinomenine and magnoflorine, which exhibit linear kinetic characteristics within a set dose range, and the rheumatoid arthritis pathological state is more conducive to the absorption and efficacy of sinomenine. The results of this study demonstrate the rationality of the clinical application of the QWTB.     

Differential pharmacokinetics and the brain distribution of morphine and ephedrine constitutional isomers in rats after oral administration with Keke capsule using rapid‐resolution LC–MS/MS

Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid‐resolution LC–MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r² > 0.99). The intra‐ and interday assay variability was less than 15% for all analytes, and the accuracy was between ?8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine.     

δ13C, δ15N and δ2H isotope ratio mass spectrometry of ephedrine and pseudoephedrine: application to methylamphetamine profiling

Conventional chemical profiling of methylamphetamine has been used for many years to determine the synthetic route employed and where possible to identify the precursor chemicals used. In this study stable isotope ratio analysis was investigated as a means of determining the origin of the methylamphetamine precursors, ephedrine and pseudoephedrine. Ephedrine and pseudoephedrine may be prepared industrially by several routes. Results are presented for the stable isotope ratios of carbon (δ¹³C), nitrogen (δ¹⁵N) and hydrogen (δ²H) measured in methylamphetamine samples synthesized from ephedrine and pseudoephedrine of known provenance. It is clear from the results that measurement of the δ¹³C, δ¹⁵N and δ²H stable isotope ratios by elemental analyzer/thermal conversion isotope ratio mass spectrometry (EA/TC‐IRMS) in high‐purity methylamphetamine samples will allow determination of the synthetic source of the ephedrine or pseudoephedrine precursor as being either of a natural, semi‐synthetic, or fully synthetic origin. Copyright © 2009 Commonwealth of Australia. Published by John Wiley & Sons, Ltd.     

Effect of Ephedrine and Its Derivatives in KML Cell Culture and on Tumor Strains of Animals

The cytotoxic activity and the ability to inhibit growth of experimental animal tumors of about 30 ephedrine and pseudoephedrine derivatives were studied in KML cell culture. It was found that the chemical structure and the biological activity are related. Four active chlorinated ephedrine and pseudoephedrine derivatives, including N-(-chloroethyl)- and N-nitroso-groups, were found in vitro and in vivo systems and may be promising for antitumor preparations.     

Simultaneous determination of paeoniflorin from total glucosides of paeony in Sprague–Dawley rats and spontaneously hypertensive rats by high‐performance liquid chromatography–tandem mass spectrometry: in vivo and in vitro studies

Paeoniflorin is a well‐known monoterpene glucoside in the herbal drug that exhibits a number of biological activities. The pharmacokinetic characteristics of paeoniflorin from total glucosides of paeony in spontaneously hypertensive rats (SHR) are still unclear. It is essential to investigate the in vivo and in vitro pharmacokinetic differences of paeoniflorin from total glucosides of paeony in Sprague–Dawley (SD) and SHR. The in vivo pharmacokinetic data were analyzed using DAS 2.0 software and the in vitro metabolic characteristics were measured using rat hepatic microsomes. The concentration of paeoniflorin in biological samples was determined using high‐performance liquid chromatography–electrospray ionization tandem mass spectrometry method, which showed good precision and stability. The plasma concentration–time profiles of paeoniflorin following oral administration of total glucosides of paeony showed a single peak and there were significant differences in the mean values of AUC_(0–t), AUC_(0–∞), CL_z/F and T_max between SD and SHR (p < 0.05). The metabolic rate of paeoniflorin from total glucosides of paeony was slower in SHR than in SD rats (p < 0.05). The results might be useful in further applications of paeoniflorin and total glucosides of paeony. Copyright © 2016 John Wiley & Sons, Ltd.