Validated assay for the simultaneous determination of the anti-cancer agent gemcitabine and its metabolite 2',2'-difluorodeoxyuridine in human plasma by high-performance liquid chromatography with tandem mass spectrometry

A sensitive and specific high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay for the quantitative determination of gemcitabine (dFdC) and its metabolite 2',2'-difluorodeoxyuridine (dFdU) is presented. A 200-microL aliquot of human plasma was spiked with a mixture of internal standards, didanosine, lamivudine and fludarabine, and extracted using solid-phase extraction. Dried extracts were reconstituted in 1 mM ammonium acetate/acetonitrile (97:3, v/v) and 10-microL volumes were injected onto the HPLC system. Separation was achieved on a 150 x 2.1 mm C18 bonded phase endcapped with polar groups (Synergi Hydro-RP column) using an eluent composed of 1 mM ammonium acetate (pH 6.8)/acetonitrile (94:6, v/v). Detection was performed by positive ion electrospray ionization followed by MS/MS. The assay quantifies a range from 0.5 to 1000 ng/mL for gemcitabine and from 5 to 10,000 ng/mL for dFdU using 200 microL of human plasma sample. Validation results demonstrate that gemcitabine and dFdU concentrations can be accurately and precisely quantified in human plasma. This assay is used to support clinical pharmacologic studies with gemcitabine.     

In situ derivatization/solid-phase microextraction coupled with gas chromatography/negative chemical ionization mass spectrometry for the determination of trichloroethylene metabolites in rat blood

An in situ derivatization solid-phase microextraction (SPME) method has been developed for the determination of the trichloroethylene (TCE) metabolites, trichloroacetic acid (TCA), dichloroacetic acid (DCA) and trichloroethanol (TCOH), in rat blood. The analytical procedure involves derivatization of TCA and DCA to their ethyl esters with acidic ethanol, headspace sampling using SPME, and gas chromatography/negative chemical ionization mass spectrometry (GC/NCI-MS) determination. Parameters affecting both derivatization efficiency and the headspace SPME procedure, such as the concentration of sulfuric acid, amount of ethanol, derivatization-extraction temperature and time, sample preheating time, agitator speed and desorption conditions, were optimized. The method showed good linearity over the range of 1-1000 ng/mL in rat blood for each metabolite with correlation coefficients (R(2)) higher than 0.99. The intra-day and inter-day precision and accuracy were less than 10%. The relative recoveries for all analytes were greater than 84%. Validation results demonstrated that selected ion monitoring of the (35)Cl and (37)Cl isotopes using NCI resulted in reliable and sensitive quantitation of all three TCE metabolites. This validated method was successfully applied to study the toxicokinetic behavior of TCE metabolites following a 1 mg/kg oral dose of TCE.     

High performance liquid chromatography/electrospray tandem mass spectrometry for phenothiazines with heavy side chains in whole blood

Eleven phenothiazine derivatives with heavy side chains contained in human whole blood have been analyzed by high-performance liquid chromatography (HPLC)/electrospray (ES) tandem mass spectrometry (MS). All compounds gave the base peaks due to [M + 1](+) by HPLC/ES single MS. The product ions formed from each quasi-molecular ion by HPLC/ES tandem MS showed the base peaks due to side chains liberated. The mass chromatography of HPLC/ES tandem MS showed much higher sensitivity than that of HPLC/ES single MS for phenothiazines spiked to whole blood. Therefore, regression equations, detection limits, recovery rates and reproducibility were studied for thiethylperazine, clospirazine and flupentixol spiked to human whole blood by means of mass chromatography of HPLC/ES tandem MS. The three compounds showed good linearity in the range of 2-40 ng/mL with a detection limit of about 0.5 ng/mL. Recoveries of the three compounds spiked to whole blood (2 and 8 ng added to 1 mL whole blood) were 43.4-72.5 %; the coefficients of intraday and interday variations were 3.7-9.3 and 12.6-17.9 %, respectively. Thiethylperazine, clospirazine and flupentixol in whole blood could actually be determined with sufficient sensitivity 3 and 6 h after oral administration of 5-10 mg of each compound in a volunteer.     

A new metabolite of nodakenetin by rat liver microsomes and its quantification by RP‐HPLC method

The biotransformation of nodakenetin (NANI) by rat liver microsomes in vitro was investigated. Two major polar metabolites were produced by liver microsomes from phenobarbital‐pretreated rats and detected by reversed‐phase high‐performance liquid chromatography (RP‐HPLC) analysis. The chemical structures of two metabolites were firmly identified as 3′(R)‐hydroxy‐nodakenetin‐3′‐ol and 3′(S)‐hydroxy‐nodakenetin‐3′‐ol, respectively, on the basis of their ¹H‐NMR, MS and optical rotation analysis. The latter was a new compound. A sensitive, selective and simple RP‐HPLC method has been developed for the simultaneous determination of NANI and its two major metabolites in rat liver microsomes. Chromatographic conditions comprise a C₁₈ column, a mobile phase with MeOH‐H₂O (40 : 60, v/v), a total run time of 40 min, and ultraviolet absorbance detection at 330 nm. In the rat heat‐inactivated liver microsomal supernatant, the lower limits of detection and quantification of metabolite I, metabolite II and NANI were 5.0, 2.0, 10.0 ng/mL and 20.0, 5.0, 50.0 ng/mL, respectively, and their calibration curves were linear over the concentration range 50–400, 20–120 and 150–24000 ng/mL, respectively. The results provided a firm basis for further evaluating the pharmacokinetics and clinical efficacy of NANI. Copyright © 2009 John Wiley & Sons, Ltd.     

A simple and sensitive assay for the quantitative analysis of rivastigmine and its metabolite NAP 226-90 in human EDTA plasma using coupled liquid chromatography and tandem mass spectrometry

A sensitive and specific high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay for the determination of rivastigmine and its major metabolite NAP 226-90 is presented. A 100 microL plasma aliquot was spiked with a structural analogue of rivastigmine as internal standard (PKF214-976-AE-1) and proteins were precipitated by adding 200 microL of methanol. After centrifugation a volume of 100 microL of the clear supernatant was mixed with 100 microL of methanol/water (30:70, v/v) and volumes of 25 microL were injected onto the HPLC system. Separation was acquired on a 150 x 2.0 mm i.d. Gemini C18 column using a gradient system with 10 mM ammonium hydroxide and methanol. Detection was performed by using a turboionspray interface and positive ion multiple reaction monitoring by tandem mass spectrometry. The assay quantifies rivastigmine from 0.25 to 50 ng/mL and its metabolite NAP 226-90 from 0.50 to 25 ng/mL, using human plasma samples of 100 microL. Validation results demonstrate that rivastigmine and metabolite concentrations can be accurately and precisely quantified in human EDTA plasma. This assay is now used to support clinical pharmacologic studies with rivastigmine.     

A high-throughput liquid chromatography/tandem mass spectrometry method for simultaneous quantification of a hydrophobic drug candidate and its hydrophilic metabolite in human urine with a fully automated liquid/liquid extraction

ABT-869 (A-741439) is an investigational new drug candidate under development by Abbott Laboratories. ABT-869 is hydrophobic, but is oxidized in the body to A-849529, a hydrophilic metabolite that includes both carboxyl and amino groups. Poor solubility of ABT-869 in aqueous matrix causes simultaneous analysis of both ABT-869 and its metabolite within the same extraction and injection to be extremely difficult in human urine. In this paper, a high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method has been developed and validated for high-speed simultaneous quantitation of the hydrophobic ABT-869 and its hydrophilic metabolite, A-849529, in human urine. The deuterated internal standards, A-741439D(4) and A-849529D(4), were used in this method. The disparate properties of the two analytes were mediated by treating samples with acetonitrile, adjusting pH with an extraction buffer, and optimizing the extraction solvent and mobile phase composition. For a 100 microL urine sample volume, the lower limit of quantitation was approximately 1 ng/mL for both ABT-869 and A-849529. The calibration curve was linear from 1.09 to 595.13 ng/mL for ABT-869, and 1.10 to 600.48 ng/mL for A-849529 (r2 > 0.9975 for both ABT-869 and A-849529). Because the method employs simultaneous quantification, high throughput is achieved despite the presence of both a hydrophobic analyte and its hydrophilic metabolite in human urine.     

Simultaneous determination of fenpropimorph and the corresponding metabolite fenpropimorphic acid in soil

Summary An analytical procedure for the simultaneous determination of fenpropimorph and its main metabolite fenpropimorphic acid in soil is reported. Extraction with acetone/water (2:1), liquid/liquid partition with dichloromethane and clean-up using gel permeation chromatography is employed to concentrate the analytes. Methylation of the polar metabolite is absolutely required for GC/MS and GC/NPD. The parent compound fenpropimorph is not influenced by this derivatization step. The detection limits are 0.005 mg/kg for fenpropimorph and 0.010 mg/kg for fenpropimorphic acid.     

Simultaneous determination of a drug candidate and its metabolite in rat plasma samples using ultrafast monolithic column high-performance liquid chromatography/tandem mass spectrometry

An ultrafast bioanalytical method using monolithic column high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) was evaluated for the simultaneous determination of a drug discovery compound and its metabolite in plasma. Baseline separation of the two compounds was achieved with run times of 24 or 30 s under isocratic or gradient conditions, respectively. The monolithic column HPLC/MS/MS system offers shorter chromatographic run times by increasing flow rate without sacrificing separation power for the drug candidate and its biotransformation product (metabolite). In this work, the necessity for adequate chromatographic resolution was demonstrated because the quantitative determination of the drug-related metabolism product was otherwise hampered by interference from the dosed drug compound. The chromatographic performance of a monolithic silica rod column as a function of HPLC flow rates was investigated with a mixture of the drug component and its synthetic metabolite. The assay reliability of the monolithic column HPLC/MS/MS system was checked for matrix ionization suppression using the post-column infusion technique. The proposed methods were successfully applied to the analysis of study rat plasma samples for the simultaneous quantitation of both the dosed drug and its metabolite. The analytical results obtained by the proposed monolithic column methods and the 'standard' silica particle-packed HPLC column method were in good agreement, within 10% error.     

Comparison of multiple API techniques for the simultaneous detection of microconstituents in water by on‐line SPE‐LC‐MS/MS

This study described a fully automated method using on‐line solid phase extraction of large volume injections coupled with high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) to simultaneously detect a group of recalcitrant microconstituents (pharmaceuticals and personal care products, steroid hormones and sterols) in aqueous matrices. Samples (1 mL to 20 mL) were loaded to the preconcentration column at 1 mL/min, and the column was washed with 1000 μL of 25% methanol in LC/MS water to remove polar and ionic interferences before LC‐MS/MS analysis. Three different atmospheric pressure ionization (API) techniques, including photoionization (APPI) with four different dopants (acetone, anisole, chlorobenzene and toluene), heated electrospray ionization (HESI) and atmospheric pressure chemical ionization (APCI), were evaluated on the basis of method detection limits (MDLs) and recoveries from different aqueous matrixes. Results indicated that APPI with toluene as dopant was the most sensitive ionization method for the majority of the analytes. When using 5 mL of sample, MDLs for pharmaceuticals and personal care products, including carbamazepine, DEET, caffeine, naproxen, acetaminophen and primidone, were between 0.3 ng/L and 15 ng/L. MDLs of hormones, including testosterone, equilenin, progesterone, equilin, 17β‐estradiol, 17α‐ethynylestradiol, estrone, androsterone, mestranol and estriol, were between 1.2 ng/L and 37 ng/L. The combination of APPI with dopant allowed the detection of two difficult to ionize fecal related sterols, such as coprostan‐3‐ol and coprostan‐3‐one with MDLs of 5.4 ng/L and 11 ng/L, respectively. Calculated MDLs are more than adequate for analysis of wastewater using 1 to 5 mL sample size and for surface waters using up to 20 mL sample size. Copyright © 2012 John Wiley & Sons, Ltd.     

Liquid chromatographic high-throughput analysis of the new ultra-short acting hypnotic 'HIE-124' and its metabolite in mice serum using a monolithic silica column

For the first time, a fast, high-performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of the new ultra-short hypnotic HIE-124 and its metabolite in mice serum. Each compound, together with carbamazepine (internal standard) was extracted from the serum matrix using liquid-liquid extraction (LLE). Chromatographic resolution of the analytes was performed on a Chromolith Speed Rod monolithic silica column (100 mm × 4.6 mm i.d.) under isocratic conditions using a mobile phase of 65:35 (v/v), 20 mM phosphate buffer (pH 7.0 adjusted with phosphoric acid)-acetonitrile. The elution of the analytes were monitored at 240 nm and conducted at ambient temperature. Because of high column efficiency the mobile phase was pumped at a flow rate of 2.5 mL min(-1). The total run time of the assay was 2 min. The method was validated over the range of 60-2000 ng mL(-1) for HIE-124 and 200-1600 ng mL(-1) for the metabolite (r(2) = 0.99). The limit of detection (LOD) for HIE-124 and its metabolite were 20 ng mL(-1) and 65 ng mL(-1), respectively. The proposed method was validated in compliance with ICH guidelines, in terms of accuracy, precision, limits of detection and quantitation and other aspects of analytical validation. The developed method could be used for the trace analyses of HIE-124 and its metabolite in serum and was finally used for the pharmacokinetic study investigation of HIE-124 in mice serum.     

High-throughput quantification for a drug mixture in rat plasma-a comparison of Ultra Performance liquid chromatography/tandem mass spectrometry with high-performance liquid chromatography/tandem mass spectrometry

A quantitative Ultra Performance liquid chromatography/tandem mass spectrometry (UPL/MS/MS) protocol was developed for a five-compound mixture in rat plasma. A similar high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) quantification protocol was developed for comparison purposes. Among the five test compounds, three preferred positive electrospray ionization (ESI) and two preferred negative ESI. As a result, both UPLC/MS/MS and HPLC/MS/MS analyses were performed by having the mass spectrometer collecting ESI multiple reaction monitoring (MRM) data in both positive and negative ion modes during a single injection. Peak widths for most standards were 4.8 s for the HPLC analysis and 2.4 s for the UPLC analysis. There were 17 to 20 data points obtained for each of the LC peaks. Compared with the HPLC/MS/MS method, the UPLC/MS/MS method offered 3-fold decrease in retention time, up to 10-fold increase in detected peak height, with 2-fold decrease in peak width. Limits of quantification (LOQs) for both HPLC and UPLC methods were evaluated. For UPLC/MS/MS analysis, a linear range up to four orders of magnitude was obtained with r2 values ranging from 0.991 to 0.998. The LOQs for the five analytes ranged from 0.08 to 9.85 ng/mL. Three levels of quality control (QC) samples were analyzed. For the UPLC/MS/MS protocol, the percent relative standard deviation (RSD%) for low QC (2 ng/mL) ranged from 3.42 to 8.67% (N = 18). The carryover of the UPLC/MS/MS protocol was negligible and the robustness of the UPLC/MS/MS system was evaluated with up to 963 QC injections.     

Simultaneous quantitation of enalapril and enalaprilat in human plasma by 96-well solid-phase extraction and liquid chromatography/tandem mass spectrometry

A sensitive and rapid method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) combined with rapid solid-phase extraction (SPE) has been developed and validated for the quantitative determination of enalapril and its active metabolite enalaprilat in human plasma. After addition of internal standard to human plasma, samples were extracted by 96-well SPE cartridge. The extracts were analyzed by HPLC with the detection of the analyte in the multiple reaction monitoring (MRM) mode. This method for the simultaneous determination of enalapril and enalaprilat was accurate and reproducible, with respective limits of quantitation of 0.2 and 1.0 ng/mL in plasma. The standard calibration curves for both enalapril and enalaprilat were linear (r(2) = 0.9978 and 0.9998) over the concentration ranges 0.2-200 and 1.0-100 ng/mL in human plasma, respectively. The intra- and inter-day precision over the concentration range for enalapril and enalaprilat were lower than 13.3 and 15.4% (relative standard deviation, %RSD), and accuracy was between 89.2-105.0 and 91.9-104.7%, respectively.     

Determination of long-acting release octreotide, an octapeptide analogue of somatostation, in human plasma by liquid chromatography/tandem mass spectrometry

A sensitive and selective method for the determination of long-acting released octreotide in human plasma has been developed based on liquid chromatography/tandem mass spectrometry (LC/MS/MS). Octreotide and the internal standard, triptorelin, were precipitated from the matrix, washed with dichloromethane and subsequently separated by reversed-phase high-performance liquid chromatography (HPLC) employing a 1% formic acid/methanol gradient system. Detection was by electrospray ionization mass spectrometry in the positive ion mode using multiple-reaction monitoring. The assay was linear in the concentration range 0.0500-50.0 ng/mL with intra- and inter-day precision (as relative standard deviation) of <2.95% and <8.37%, respectively. The limit of detection was 0.0200 ng/mL. The method was applied to a pharmacokinetic study of long-acting released octreotide in healthy volunteers given an intramuscular injection containing 20 mg octreotide.     

Determination of (R)- and (S)-phenprocoumon in human plasma by enantioselective liquid chromatography/electrospray ionisation tandem mass spectrometry

Phenprocoumon is a commonly used oral anticoagulant of the coumarin type, and has found extensive clinical use in the treatment of thrombophlebitis, pulmonary embolism and atrial fibrillation. In the course of a clinical study to investigate the influence of genetic polymorphisms of the CYP2C9 enzyme on phenprocoumon metabolism, we developed a new enantioselective liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/MS/MS) method to quantify (R)- and (S)-phenprocoumon in human plasma. HPLC separation of the enantiomers was achieved on a Chira-Grom-2 column under isocratic conditions using a water/acetonitrile/formic acid eluent. For detection and quantification a triple-quadrupole MS system was used in the selected reaction monitoring (SRM) mode. As an internal standard the structurally homologous compound warfarin was chosen. The detector response was linear with a correlation coefficient of 0.988-0.999 for (R)-phenprocoumon and 0.989-0.999 for (S)-phenprocoumon in the investigated concentration range between 62.5 and 1000 ng/mL (per enantiomer). The limit of detection (LOD) was 12.5 ng/mL.     

Determination of proanthocyanidins in fresh grapes and grape products using liquid chromatography with mass spectrometric detection

Fresh grapes and grape products, such as grape wine and grape juice, were analyzed for proanthocyanidins (PACs) using liquid chromatography with electrospray ionization mass spectrometric (MS) detection. PACs were successfully separated and analyzed on the basis of their protonated molecules, allowing the identification of PACs in different degrees of polymerization from monomers to oligomers (up to 7 units), and in various isomeric forms. Using reversed-phase high-performance liquid chromatography (HPLC) combined with MS detection, the PAC monomers, (+)-catechin (C), (-)-epicatechin (EC), (-)-catechin gallate (CG), and (-)-epicatechin gallate (ECG), were successfully quantified using selected ion monitoring (SIM) mode. Standard curves were fitted for each PAC ranging from 43.8 to 5600 ng/mL for C, from 42.2 to 5400 ng/mL for EC, from 36.7 to 4700 ng/mL for CG, and from 39.8 to 5100 ng/mL for ECG. Good linearity (r2>0.999) was achieved for each analyte. The accuracy and precision (RSD) were within 10% (n=8) at the limit of detection. This method allows direct quantification of monomeric PACs in fresh grapes and grape-derived products. Additionally, flow injection analysis (FIA) was applied to estimate the concentration levels of PAC oligomers by comparing their FIA-MS peak areas, which were well correlated (r2=0.936) to the total concentrations of PAC monomers.     

Development of a method for simultaneous determination of eflucimibe and its three major metabolites in rat plasma by liquid chromatography/electrospray tandem mass spectrometry: a preliminary study

A high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry (HPLC/ESI-MS/MS) method has been developed for the simultaneous determination of eflucimibe, a powerful acyl-coenzyme A cholesterol O-acyltransferase (ACAT) inhibitor, and its main metabolites, in plasma. The ESI and MS/MS parameters were investigated and optimised for each of the four compounds in the positive ion mode. Plasma samples were deproteinised by precipitation with acetonitrile and directly analysed by HPLC/ESI-MS/MS in less than 4 min. Quantitation was performed in the multiple reaction monitoring (MRM) mode for highest sensitivity, selecting the protonated molecules [M+H](+) as precursor ions. The method was demonstrated to be specific and sensitive, and a linear response was observed within a 1-25 ng/mL concentration range. Correlation coefficients (r(2)) greater than 0.9960 were obtained by least-squares regression, and limits of detection down to 0.2 ng/mL were calculated. Therefore, this HPLC/ESI-MS/MS method appears to be an efficient tool, able to provide valuable information for a pharmacological purpose.     

Identification and quantification of glutathione adducts of clozapine using ultra-high-performance liquid chromatography with orthogonal acceleration time-of-flight mass spectrometry and inductively coupled plasma mass spectrometry

The application of sulphur-specific detection via ultra-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (UPLC/ICPMS) to detect and quantify the glutathione (GSH)-adducts produced via the in vitro formation of reactive metabolites is demonstrated. The adducts were formed in human liver microsomes supplemented with unlabelled GSH for clozapine. The calculation of adduct concentration was performed via comparison of the peak areas to calibration curves constructed from omeprazole, a sulphur-containing compound over the range of 0.156 to 15.62 μM of sulphur with a detection limit of 1.02 ng of sulphur on-column. Identification of the adducts was performed using conventional UPLC/time-of-flight (TOF)-MS with the calculation of clozapine intrinsic clearance carried out by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). The use of ICPMS in this way appears to offer a novel, rapid and sensitive means of determining the quantity of GSH conjugates with the combined adducts producing 0.9 μM of reactive metabolite out of a total of 3.5 μM of metabolites. The GSH adduct therefore represents 26% of this total produced as a result of the metabolism of drug to reactive species.     

Rapid screening of drugs of abuse and their metabolites by gas chromatography/mass spectrometry: application to urinalysis

This paper describes a rapid gas chromatographic/mass spectrometric (GC/MS) screening method for the detection of drugs of abuse and/or their metabolites in urine. Synthetic stimulants, opiates, cocaine metabolites, cannabinoids--and specifically the acid metabolite of tetrahydrocannabinol (THC-COOH)--can be simultaneously extracted by a single liquid/liquid separation step, at alkaline pH, and assayed as trimethylsilyl derivatives by GC/MS in SIM (selected ion monitoring) mode. All the analytes show a good linearity (R2 > 0.99 for most of the considered substances) in the range 25-1000 ng/mL, with a good reproducibility of both the retention times (CV% <0.7) and the relative abundances of the characteristic diagnostic ions (CV% <13). The limit of detection (LOD) of the method is 25 ng/mL of target compound in human urine for most of the substances investigated, 3 ng/mL for THC-COOH, and 10 ng/mL for norbuprenorphine. Validation of the method allows its application to different fields of forensic analytical toxicology, including antidoping analysis.     

The determination of melamine in muscle tissue by liquid chromatography/tandem mass spectrometry

In early 2007 it was determined that the compound melamine, suspected of having been involved in the deaths of numerous pets, had been fed to hogs intended for human consumption. This report describes a method for the analysis of melamine in porcine muscle tissue using solid-phase extraction (SPE) and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Melamine was extracted in 50% acetonitrile in water. Homogenates were centrifuged and supernatants were acidified and washed with methylene chloride. The aqueous extracts were cleaned up using mixed-mode C8/strong cation exchange SPE and then concentrated, fortified with a stable isotope-labeled analog of melamine, and analyzed by HPLC/MS/MS. Gradient HPLC separation was performed using an ether-linked phenyl column with ammonium acetate/acetic acid and acetonitrile as the mobile phase. Multiple reaction monitoring (MRM) mode of two precursor-product ion transitions for melamine and one for the internal standard was used. A five point calibration curve ranging from 50 to 2000 ng/mL of melamine in solvent was used to establish instrument response. The method was validated by analysis of seven replicate porcine muscle tissue samples fortified with 10 ng/g of melamine. The mean recovery for the seven replicates was 83% with 6.5% relative standard deviation and the calculated method detection limit was 1.7 ng/g.     

高效液相色谱-离子阱质谱法测定人血浆中的头孢拉定和青霉素G

目前,β-内酰胺类抗生素在临床抗感染药物中占有十分突出的地位,但在近年来的药品不良反应报告中,抗生素类药物引起的不良反应也占据了很高的比例,其中有我国生活环境影响、感染性疾病多的客观因素,但病人用药盲目性大、医生用药随意性多的问题也普遍存在。因此,进一步加强对抗生素类药物的监测,开发快速有效的分析测试方法显得十分重要。本文基于实际全血未知样品,开发了基于固相萃取及液质联用技术,快速准确地对血液中青霉素G及头孢拉定进行定性及质谱定量分析的检测方法。