Correlation analysis between tigecycline therapeutic concentration monitoring and adverse reactions

doi:10.12092/j.issn.1009-2501.2026.09.010

Abstract

Abstract:

AIM: To establish a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of tigecycline in human plasma, which was used to study the pharmacokinetic profile in patients and to investigate the correlation between its blood concentration and drug-induced hepatic injury and coagulation dysfunction. METHODS: Plasma was processed by protein precipitation, separated on an Eclipse Plus C₁₈ column, eluted by a 0.1% formic acid water-methanol gradient, with Reserpine as an internal standard, at a flow rate of 0.3 mL/min and detected in the positive ion mode and examined the method properties. Subsequently, clinical data with plasma samples were collected from patients using tigecycline between June 2024 and June 2025 (n=72). The groups were grouped according to whether or not an adverse reaction (ADR) occurred, the differences in blood concentrations between the two groups were compared, and the blood concentration breakpoints at which ADRs occurred were determined using subject's work characterization curve (ROC) analysis, and the sensitivity, specificity, and area under the curve (AUC) were calculated. RESULTS: The linear range of the proposed method was 50-5000 ng/mL, and the precision, accuracy and stability values were less than 10%, which met the requirements of clinical testing. The ROC curve showed that the fold point of tigecycline causing liver injury was 515.34 ng/mL, and that of coagulation dysfunction was 243.59 ng/mL. CONCLUSION: The HPLC-MS/MS of tigecycline in human plasma was successfully established, and the tigecycline blood concentration is related to the cause of liver injury and coagulation dysfunction. It is recommended that blood concentration monitoring combined with liver function and coagulation indicators should be applied clinically to ensure medication safety.

Key words: tigecycline, therapeutic drug monitoring, HPLC-MS/MS, pharmacokinetics, liver injury, coagulation-disorders

CLC Number:

R969.3

Shiya WU, Xiaodan LIU, Yan HU, Qi LIN. Correlation analysis between tigecycline therapeutic concentration monitoring and adverse reactions[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(9): 1238-1248.

Figures/Tables 11

References 33

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Compound	Ion pair type	Precursor Ion (m/z)	Product Ion (m/z)	Exit voltage (V)	Collision energy (eV)
TGC	Quantitative ion-pairing	586.3	513.1	180	30
TGC	Qualitative ion pair	586.3	569.2	180	20
Reserpine	Quantitative ion-pairing	609.2	195.0	110	40
Reserpine	Qualitative ion pair	609.2	173.4	110	50

Compound	Ion pair type	Precursor Ion (m/z)	Product Ion (m/z)	Exit voltage (V)	Collision energy (eV)
TGC	Quantitative ion-pairing	586.3	513.1	180	30
TGC	Qualitative ion pair	586.3	569.2	180	20
Reserpine	Quantitative ion-pairing	609.2	195.0	110	40
Reserpine	Qualitative ion pair	609.2	173.4	110	50

Nominal Concentration (ng/mL)		Run 1	Run 2	Run 3
Nominal Concentration (ng/mL)		?
50		0.0104897	0.0112690	0.0115818
100		0.0206517	0.0211542	0.0219776
200		0.0435247	0.0422220	0.0447260
500		0.0892320	0.0952995	0.0871738
1000		0.1692829	0.1533830	0.1636522
2000		0.3422944	0.3192495	0.3483906
3000		0.5121539	0.5044906	0.4950652
5000		0.8779048	0.8635990	0.8622892
Parameter	a	0.0001736	0.0001703	0.0001700
	b	0.001016	?0.0009	0.002409
	r	0.9995	0.9982	0.9991

Nominal Concentration (ng/mL)		Run 1	Run 2	Run 3
Nominal Concentration (ng/mL)		?
50		0.0104897	0.0112690	0.0115818
100		0.0206517	0.0211542	0.0219776
200		0.0435247	0.0422220	0.0447260
500		0.0892320	0.0952995	0.0871738
1000		0.1692829	0.1533830	0.1636522
2000		0.3422944	0.3192495	0.3483906
3000		0.5121539	0.5044906	0.4950652
5000		0.8779048	0.8635990	0.8622892
Parameter	a	0.0001736	0.0001703	0.0001700
	b	0.001016	?0.0009	0.002409
	r	0.9995	0.9982	0.9991

Batch	LLOQ (50 ng/mL)	Accuracy	LQC1 (150 ng/mL)	Accuracy	LQC2 (750 ng/mL)	Accuracy	MQC (3000 ng/mL)	Accuracy	HQC (4500 ng/mL)	Accuracy
First batch	49.42	98.84	152.72	101.81	757.74	101.03	3070.49	102.35	4491.45	99.81
	51.13	102.26	150.63	100.42	756.50	100.87	3015.87	100.53	4508.53	100.19
	48.73	97.46	156.20	104.13	747.38	99.65	3064.82	102.16	4509.69	100.22
	49.58	99.16	151.84	101.23	757.59	101.01	3038.98	101.30	4517.66	100.39
	52.13	104.26	148.94	99.29	756.22	100.83	3073.57	102.45	4588.20	101.96
Mean	50.20		152.07		755.09		3052.75		4523.11
SD	1.39		2.71		4.36		24.72		37.62
Intra-batch CV%	2.77		1.78		0.58		0.81		0.83
Intra-batch Accuracy (%)	0.40		1.38		3.39		1.76		0.51
Second batch	51.70	103.40	152.91	101.94	748.01	99.73	3081.22	102.71	4422.70	98.28
	49.97	99.94	149.16	99.44	747.89	99.72	3059.91	102.00	4518.38	100.41
	52.32	104.64	146.54	97.69	759.12	101.22	3016.10	100.54	4468.88	99.31
	49.12	98.24	151.29	100.86	755.76	100.77	2946.45	98.22	4572.92	101.62
	52.36	104.72	149.57	99.71	750.76	100.10	2942.75	98.09	4526.11	100.58
Mean	51.09		149.89		752.31		3009.29		4501.80
SD	1.47		2.39		4.97		63.56		57.59
Intra-batch CV%	2.88		1.60		0.66		2.11		1.28
Intra-batch Accuracy (%)	2.19		?0.07		1.54		0.31		0.04
Third batch	48.35	96.70	156.43	104.29	758.76	101.17	3097.68	103.26	4591.62	102.04
	53.94	107.88	156.02	104.01	745.76	99.43	3085.69	102.86	4581.90	101.82
	54.09	108.18	148.81	99.21	745.76	99.43	2900.04	96.67	4486.38	99.70
	53.09	106.18	148.59	99.06	757.76	101.03	2972.74	99.09	4527.42	100.61
	53.04	106.08	153.26	102.17	754.76	100.63	3002.13	100.07	4594.60	102.10
Mean	52.50		152.62		752.56		3011.66		4556.38
SD	2.37		3.78		6.38		82.07		47.68
Intra-batch CV%	4.51		2.48		0.85		2.73		1.05
Intra-batch Accuracy (%)	5.00		1.75		1.71		0.39		1.25
Mean Calculated Concentration	51.26		151.53		753.32		3024.56		4527.10
Inter-batch CV%	3.77		2.01		0.67		2.01		1.11
Intra-batch accuracy (%)	2.53		1.02		2.21		0.82		0.60