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Objective: A sensitive and rapid ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was successfully applied to the determination of 10 alkaloids in beagle dog plasma following a single oral dose of Xiatianwu capsules and enteric‐coated capsules, with theophylline serving as the internal standard (IS). Methods: Plasma samples were preprocessed using liquid–liquid extraction (LLE) with ethyl acetate ahead to separation using a gradient elution procedure on a Waters ACQUITY UPLC HSS T3 column (1.8 μm, 100 × 2.1 mm). The mobile phase was composed of 0.1% formic acid solution and acetonitrile at the flow rate of 0.3 ml/min. Multiple reaction monitoring (MRM) was used to determine the analytes in the positive ion mode. Results: The calibration curves for 10 analytes demonstrated a high degree of linearity (r ≥ 0.9920). The lower limit of quantification (LLOQ) values for 10 alkaloids were all more than 1.074 ng/ml, and matrix effects varied from 94.25% to 106.15%. The mean extraction recovery of quality control samples at low (LQC), medium (MQC) and high (HQC) concentrations, as well as IS, was all more than 76.60%. The intra‐day and inter‐day precision (RSD) also satisfied the requirement. Simultaneously, the variation of assay accuracies (RE) was between 13.05% and 9.38%. Conclusion: The test was validated in accordance with regulatory bioanalytical guidelines and was found to be suitable for use in a pharmacokinetic investigation of these compounds in beagle dogs after oral administration of Xiatianwu general capsules and enteric‐coated capsules. The Cmax of 10 alkaloids ranged from 52.61 to 192.46 ng/ml after oral administration of Xiatianwu capsules, and from 67.50 to 247.36 ng/ml. The Tmax was between 0.59 and 1.33 h of Xiatianwu capsules, and between 1.08 and 2.00 h of enteric‐coated capsules. The t1/2 ranged from 3.18 to 7.47 h of general capsules, and from 6.01 to 11.36 h. AUC0‐t ranged from 181.06 to 722.74 ng·h/ml of Xiatianwu capsules, and from 275.03 to 884.17 ng·h/ml of enteric‐coated capsules. The Cmax of enteric‐coated capsules were significantly increased except for tetrahydropalmatine and berberine. Tmax of general capsules were less than 1 h, and of enteric‐coated capsules were less than 2 h. The t1/2 of dehydrocorydaline, palmatine, tetrahydrojatrorrhizine, jatrorrhizine and coptisine in enteric‐coated capsules was longer than that in ordinary capsule. The AUC0‐t and AUC0‐∞ of bicuculline, dehydrocorydaline, protopine, magnoflorine, tetrahydrojatrorrhizine, jatrorrhizine, berberine and coptisine were all significantly higher in enteric‐coated capsules. [ABSTRACT FROM AUTHOR]

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ziyuglycoside I (I), 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester (II), 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (III), rosamultin (IV), 1β-hydroxyeuscaphic acid (V) and alpinoside (VI) in rats after oral administration of Sanguisorba officinalis L. (S. officinalis) extract. The 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside in rat plasma were the first report in the pharmacokinetics study in the present study. The analytes were quantified using the multiple reaction monitoring (MRM) mode with the electrospray ion source in positive electrospray ionization. Plasma was extracted with ethyl acetate via liquid–liquid extraction. Bifendate was used as internal standard (IS). The current method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability. The lower limits of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside were 6.1, 4.9, 1.3, 3.8, 1.5 and 5.7 ng/mL, respectively. Intra-day and inter-day precision and the accuracy of the assay were in range from −9.48 to 12.74%. The extraction recoveries of analytes and bifendate (IS) from rat plasma ranged from 77.17% to 92.48%. Six compounds could be rapidly absorbed into blood (Tmax, 0.58–1.58 h), and then eliminated relatively slowly (t1/2, 6.86–11.63 h). The pharmacokinetic results might contribute to further guide the clinical application of S. officinalis. [ABSTRACT FROM AUTHOR]

A rapid and sensitive Ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of fourteen alkaloids in beagle dog plasma after a single oral dose of the Corydalis bungeana Turcz (C. bungeana) extract selected bifendate as the internal standard (IS). The plasma samples were preprocessed by liquid-liquid extraction (LLE) with aether before separation on an Agilent SB-C18 column (1.8 µm, 150 × 2.1 mm) using a gradient elution program. The mobile phase consists of 0.2% acetic acid and acetonitrile at the flow rate of 0.3 mL/min. In the positive ion mode, the analytes were detected by multiple reaction monitoring (MRM). The results indicated that calibration curves for fourteen analytes have good linearity (R2 = 0.9904). The lower limits of quantification (LLOQ) of fourteen alkaloids and IS were all over 4.87 ng/mL and the matrix effects ranged from 94.08% to 102.76%. The mean extraction recoveries of Quality control samples at low (LQC), medium (MQC) and high (HQC) and IS were all more than 78.03%. The intra- and inter-day precision (R.S.D.%) also met the criterion, at the same time the deviation of assay accuracies (R.E) ranged from −13.70% to 14.40%. The Tmax values of fourteen alkaloids were no more than 1 h. The range of Cmax was from 74.16 ± 8.71 to 2256 ± 255.9 ng/mL. The assay was validated in the light of the regulatory bioanalytical guidelines and proved acceptable, which was successfully applied to a pharmacokinetic study of these compounds in beagle dogs after oral administration of Corydalis bungeana Turcz extract. [ABSTRACT FROM AUTHOR]

This study has developed a sensitive and simple ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of corydaline, dehydrocorydaline, tetrahydropalmatine, protopine, palmatine, tetrahydroberberine, columbamine, berberine, coptisine and berberrubine in beagle dog plasma after the oral administration of the Corydalis yanhusuo W.T. Wang and Yuanhuzhitong tablets. Chromatographic separation was achieved on an Agilent Eclipse Plus C18 RRHD column (1.8 µm, 50 × 2.1 mm) using a gradient elution program with a mobile phase consisting of acetonitrile and water containing 0.1% formic acid at a flow rate of 0.3 mL/min. A tandem mass spectrometric detection was conducted by multiple reaction monitoring (MRM) mode via an electrospray ionization source in the positive mode. The calibration curves of all analytes showed good linear (r2 > 0.9800). The intra-day and inter-day precisions were less than 15% and the accuracies were within ±15%. The extraction recoveries conformed to the acceptable range. And there was no interference of endogenous substances in the sensitive assay method. All analytes were proven to be stable during sample storage and analysis procedures. The pharmacokinetic study indicated that the Yuanhuzhitong tablets could get a better absorption than Corydalis yanhusuo W.T. Wang. [ABSTRACT FROM AUTHOR]

Coptidis rhizoma (CR) is the dried rhizome of the ranunculaceous plant CR. For decades in China, this plant has been used to treat hypertension, hyperlipidemia, and chronic diarrhea and has been officially included in the Chinese Pharmacopoeia. The present paper presents a review of the pharmacokinetics of CR. The pharmacokinetic studies and differences of 10 alkaloids among Coptis deltoidea C. Y. cheng et Hsiao, Coptis chinensis Franch and Coptis teeta Wall. Are seldom reported. This study is the first to determine corydaline, dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine, which adopted an ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, simultaneously. Chromatographic separation was performed within 8 min by using an Agilent SB-C 18 column (150 mm × 2.1 mm, 1.8 μm) with gradient mobile phase consisting of 0.3% acetic acid water (v / v) and acetonitrile at a flow rate of 0.3 mL/min. Multiple reaction monitoring mode was used to detect the tandem mass spectrum in the positive ionization mode by electrospray ionization source. The method was fully validated to be linear over a wide concentration (r > 0.9916), and the linear concentration range was 0.195–2260 ng/mL. Intra- and interday precisions were below 14.19% and 18.56% for the 10 analytes, respectively. The accuracy ranged from −9.30% to 6.31%. The extraction recovery of the 10 alkaloids and internal standard ranged from 79.76% to 95.37%. Pharmacokinetic comparative study showed that the C max and AUC 0-∞ values of dehydrocorydaline, tetrahydropalmatine, palmatine, magnoflorine, jatrorrhizine, berberine, worenine, berberrubine, and coptisine increased significantly (p < 0.05), which was different for beagles after oral administration. The results can help determine the mechanism of action and guide clinical application of these three extracts. This validated method was successfully applied for the pharmacokinetics study of beagle plasma after oral administration of three CR extract types. Image 1 [ABSTRACT FROM AUTHOR]