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. 2018 Aug 2;23(8):1927.
doi: 10.3390/molecules23081927.

Liquid Chromatography-Tandem Mass Spectrometry Simultaneous Determination and Pharmacokinetic Study of Fourteen Alkaloid Components in Dog Plasma after Oral Administration of Corydalis bungeana Turcz Extract

Hongrui Dong  1 , Guanyun Yan  2 , Zhibin Wang  3 , Chengcui Wu  4 , Binbin Cui  5 , Yixuan Ren  6 , Chunjuan Yang  7
Affiliations

Liquid Chromatography-Tandem Mass Spectrometry Simultaneous Determination and Pharmacokinetic Study of Fourteen Alkaloid Components in Dog Plasma after Oral Administration of Corydalis bungeana Turcz Extract

Hongrui Dong et al. Molecules. .

Abstract

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.

Keywords: Corydalis bungeana Turcz; Ultra high-performance liquid chromatography-tandem mass spectrometry; alkaloids; pharmacokinetics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(1) Blank sample (without the fourteen analytes and I.S.) (2) Blank plasma spiked with the fourteen analytes and I.S. (LLOQ: 5.34/5.00/5.53/5.00/5.55/5.40/5.00/5.58/5.65/4.87/5.07/5.11/5.80/6.50 ng/mL for Z23 (A), coptisine (B), berberrubine (C), sanguinarine (D), worenine (E), berberine (F), jateorhizine (G), columbamine (H), palmatine (I), protopine (J), tetrahydropalmatine (K), corynoline (L), 8-oxocorynoline (M), acetylcorynoline (N)). (3) Blank plasma spiked with fourteen alkaloids and I.S (QCM: 133.5/125.0/138.1/125.0/138.8/135.0/125.0/139.4/141.3/121.8/126.8/127.8/145.0/162.5 ng/mL for A, B, C, D, E, F, G, H, I, J, K, L, M, N). (4) Representative MRM chromatograms of (A–N) and IS in a beagle dog plasma taken 1 h after administration of 0.12 g/kg C. bungeana extract.
Figure 2
Figure 2
The concentration of fourteen alkaloids in plasma-time profiles of Z23, coptisine, berberrubine, Sanguinarine, worenine, berberine, jateorhizine, columbamine, Palmatine, protopine, tetrahydropalmatine, corynoline, 8-oxocorynoline, acetylcorynoline in beagle plasma after oral administration of C. bungeana extract. Values are expressed as mean ± SD (n = 6). The mean ± SD plasma concentration-time profiles of the fourteen alkaloids in the beagle dog plasma after oral administration of C. bungeana extract (A–D) from 0 to 3 h, respectively. (n = 6).
Figure 2
Figure 2
The concentration of fourteen alkaloids in plasma-time profiles of Z23, coptisine, berberrubine, Sanguinarine, worenine, berberine, jateorhizine, columbamine, Palmatine, protopine, tetrahydropalmatine, corynoline, 8-oxocorynoline, acetylcorynoline in beagle plasma after oral administration of C. bungeana extract. Values are expressed as mean ± SD (n = 6). The mean ± SD plasma concentration-time profiles of the fourteen alkaloids in the beagle dog plasma after oral administration of C. bungeana extract (A–D) from 0 to 3 h, respectively. (n = 6).
Figure 3
Figure 3
MS/MS fragmentation patterns of (A) 7′-(3′,4′-dihydroxyphenyl)-N-[(4-me thoxyphenyl)-ethyl]propena-mide/Z23, (B) coptisine, (C) berberrubine, (D) berberrubine, (E) worenine, (F) berberine, (G) jateorhizine, (H) columbamine, (I) palmatine, (J) protopine, (K) tetrahydropalmatine, (L) corynoline, (M) 8-oxocorynoline, (N) acetylcorynoline and (I.S).
Figure 3
Figure 3
MS/MS fragmentation patterns of (A) 7′-(3′,4′-dihydroxyphenyl)-N-[(4-me thoxyphenyl)-ethyl]propena-mide/Z23, (B) coptisine, (C) berberrubine, (D) berberrubine, (E) worenine, (F) berberine, (G) jateorhizine, (H) columbamine, (I) palmatine, (J) protopine, (K) tetrahydropalmatine, (L) corynoline, (M) 8-oxocorynoline, (N) acetylcorynoline and (I.S).
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