J.Z. Min et al., Eur. J. Mass Spectrom. 20, 477–486 (2014) Received: 6 August 2014 n Revised: 5 November 2014 n Accepted: 13 January 2015 n Publication: 21 January 2015

477

EUROPEAN JOURNAL OF MASS SPECTROMETRY

Rapid and sensitive determination of diacetylpolyamines in human fingernail by ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry Jun Zhe Min,a,b* Yuka Morota,a Ying-Zi Jiang,b Gao Li,b Dongri Jin,b Dongzhou Kang,b Hai-fu Yu,c Koichi Inoue,a Kenichiro Todorokia and Toshimasa Toyo’okaa,* a Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. E-mail: [email protected]; E-mail: [email protected] b Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China c

Fengxian Branch of Shanghai Sixth People’s Hospital, Shanghai 201400, China A rapid and sensitive ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLCESI-MS/MS) method has been developed and validated for quantitatively determining diacetylpolyamines in the human fingernail. N1,N8-diacetylspermidine (DiAct-Spd), N1,N12-diacetylspermine (DiAct-Spm) and 1,6-diaminohexane (DAH) [the internal standard (IS)] were extracted from human fingernail samples by a MeOH : 5 M HCl solution, followed by 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3benzoxadiazole (DBD-F) derivatization, and then separated on an ACQUITY BEH C18 column with a gradient elution of acetonitrile and water containing 0.1% formic acid. The derivatives of the diacetylpolyamines were fully separated within a short run time (3.0 min). The triple quadrupole mass spectrometric detection was performed in the multiple reactions monitoring (MRM) mode by the UPLCESI-MS/MS system in the positive ionization mode. MRM using the fragmentation transitions of m/z 455.20 → 100.07, 737.25 → 100.07 and 567.10 → 479.07 in the positive ESI mode was performed to quantify DiAct-Spd, DiAct-Spm and IS, respectively. The calibration curve is between 0.04 ng mL–1and 10 ng mL–1 for DiAct-Spd and DiAct-Spm. The detection limits (signal to noise ratio of five) were 5–10 pg mL–1. A good linearity was achieved from the calibration curves (r2 > 0.9999), and the intra-day and inter-day assay precisions were less than 7.06%. Furthermore, the recoveries (%) of the diacetylpolyamines spiked in the human fingernails were 79.18–97.11. The present method proved that the high sensitivity is characterized by the specificity and feasibility of the sample analysis. Consequently, the proposed method was used to analyze human fingernail samples from 15 lung-cancer patients and 22 healthy volunteers. Diacetylpolyamines were detected from the fingernails of the lung-cancer patients for the first time. The concentration of DiAct-Spd in the lung-cancer patient group tended to be higher than those in the healthy volunteers.

Keywords: human fingernail, diacetylspermidine, diacetylspermine, lung cancer, UPLC-ESI-MS/MS.

ISSN: 1469-0667 doi: 10.1255/ejms.1301

© IM Publications LLP 2014 All rights reserved

478

Rapid and Sensitive Determination of Diacetylpolyamines in the Human Fingernail by UPLC-ESI-MS/MS

Introduction Naturally occurring polyamines in mammalian cells exist in the mono or diacetylated forms. A series of enzymes converts them into spermine and spermidine.1 Owing to their positive charges, polyamines bind to macromolecules, including (deoxy)ribonucleic acid and ribonucleic acid, and their concentrations are increased in malignant and proliferating cells; this indicates that they may have potential utility as tumor markers.2 Yamaguchi et al. and Umemori et al. reported that the urinary N1,N8-diacetylspermidine (DiAct-Spd) and N1,N12diacetylspermine (DiAct-Spm) concentrations are increased in patients with pancreatobiliary, 3 colorectal and breast cancers.4,5 These observations stimulated our interest in the mechanism and significance of the generation and excretion of diacetylpolyamines under physiological conditions. To understand the physiological significance of these diacetylpolyamines and their metabolism, the detection of diacetylpolyamines in tissues, body fluids and excretions is very important. Therefore, the simultaneous determination of diacetylpolyamines has become an important task for cancer diagnosis and antitumor drug monitoring, particularly in the study of metabonomics related to diacetylpolyamines and cancer.6 Among the biological specimens screened for the diacetylpolyamine assays, noninvasive urine was the most extensively investigated.5,7 However, the inherent problems of urine specimens, such as the fluctuation in their composition during the day and hygienic practices during their collection and handling, prompted us to search for other types of noninvasive samples. In contrast, the human fingernail is relatively clean and the samples can be quickly and noninvasively collected and easily stored. According to recent reports, human nails may be used to obtain physiologic information, and may serve as a noninvasive biosample for the diagnosis of chronic diseases. Certain kinds of endogenous biogenic amino acids, intermediates of advanced glycation end products and polyamines have been detected in the human nail.8–13 However, to the best of our knowledge, a method described for the simultaneous quantitative analysis of these diacetylpolyamines in the fingernails of a lung-cancer patient has not yet been reported. It is necessary to develop a rapid, sensitive and robust method for the high-throughput determination of diacetylpolyamines in the human fingernail. Various detection methods concerning diacetylpolyamine analysis have been developed because of the importance of understanding cancer diagnosis and antitumor drug monitoring. However, the derivative procedure and enzyme-linked immunosorbent assay (ELISA) was selected since diacetylpolyamines do not contain a suitable chromophore or fluorophore group and possess the properties of low molecular weight. Analytical methods used to study these acetylpolyamines include high-performance liquid chromatography (HPLC),14–16 gas chromatography/mass spectrometry,17–19 liquid chromatography/mass spectrometry (LC-MS),7,20–24 and ELISA.2,25–27 As the simultaneous determination of very low concentrations of diacetylpolyamines in complex biological samples

without other biogenic amines or endogenous interfering is still a problem, the simultaneous determination of reported unknown diacetylpolyamines at very low concentrations in complex matrices is fairly difficult, even using the highly sensitive LC-MS method. The analysis of minor compounds in complex matrices is usually difficult because of interferences by the matrix components, even when extensive separation and clean-up procedures are applied to the sample. The present study was undertaken to develop a reliable and sensitive method for the absolute quantification of diacetylpolyamines in human fingernails. We now describe a relatively simple and sensitive UPLC-ESI-MS/MS method for determining diacetylpolyamines in human fingernails using a 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3benzoxadiazole (DBD-F) derivatization with an electrospray ionization (ESI) source in the multiple reaction monitoring (MRM) detection mode. It was used to measure diacetylpolyamines from 37 people, 15 with lung cancer and 22 healthy volunteers. Based on the contents of the diacetylpolyamines, the difference between the lung-cancer sufferers and healthy individuals was investigated in this study. It was demonstrated that a high sensitivity and wide linear concentration range was achieved using the highly efficient UPLC-ESI-MS/MS system for human fingernail samples.

Experimental

Materials and reagents

The diacetylpolyamines, i.e., N 1 ,N 8 -diacetylspermidine (DiAct-Spd: Wako, Osaka, Japan), and N1,N12-diacetylspermine 4-hydrochloride (DiAct-Spm, Wako, Osaka, Japan) were used. 1,6-Diaminohexane (DAH: Tokyo Kasei, Japan) was used as the internal standard (IS) (Figure 1). DBD-F was purchased from the Tokyo Kasei Co. (Tokyo, Japan). Formic acid [HCOOH (FA)], hydrochloric acid (HCl), trifluoroacetic acid (TFA), sodium tetraborate (Na2B4O7, borax), sodium dodecylsulfate (SDS), methanol (CH3OH) and acetonitrile (CH3CN) were of special reagent grade (Wako Pure Chemicals, Osaka, Japan). All other chemicals were of analytical reagent grade and were used without further purification. Deionized and distilled water was used throughout the study (Aquarius pwu-200 automatic water distillation apparatus, Advantec, Tokyo, Japan).

UPLC-ESI-MS/MS conditions The UPLC-ESI-MS/MS analysis was performed using a XevoTM TQ-S triple quadrupole mass spectrometer (Waters, Milford, MA) connected to an ACQUITY ultra-performance liquid chromatograph (UPLC I-class, Waters). An ACQUITY UPLC BEH C18 column [1.7 µm, 50 mm × 2.1 mm internal diameter (i.d.); Waters] was used at a flow rate of 0.4 mL min–1 and 40°C. The mobile phase A consisted of 0.1% FA in water. Mobile phase B was 0.1% FA in CH3CN and the total run time was 3.0 min. The gradient steps were as follows: 0–3.0 min, linear

J.Z. Min et al., Eur. J. Mass Spectrom. 20, 477–486 (2014) 479

Figure 1. Derivatization reaction of diacetylpolyamines with DBD-F.

gradient from 15% to 80% solvent B. The injection volume was 5 µL. The diacetylpolyamines were analyzed by UPLCESI-MS/MS in the positive-ion mode unless otherwise stated, and the MRM mode involved a switching ionization mode. The detection conditions were a capillary voltage of 3.00 kV, cone voltage of 38 V, desolvation gas flow of 1000 L h–1, cone gas flow of 150 L h–1, nebulizer gas flow of 7.0 L h–1, collision gas flow of 0.15 mL min–1, collision energy of 22 eV (DiAct-Spd), 38 eV (DiAct-Spm), or 20 eV (IS), collision cell exit potential of 5 V, and desolvation temp of 500°C. The analytical software used for the system control and data processing was (MassLynx, version 4.1).

Derivatizing the polyamines with DBD-F To 30 µL of an aqueous solution containing each of the diacetylpolyamines and DAH (IS) (2 ng mL–1), 150 µL of DBD-F in CH3CN (9.81 mg mL–1) and 120 µL of 0.1 M borax (pH 9.3) were added and vigorously mixed. Each solution was then heated at 60°C for 0 min to 120 min. The reaction solutions were filtered through a Millex-LG membrane (4 mm i.d. disk, 0.2 µm). An aliquot of the filtrate was then subjected to the UPLC-ESI-MS/MS system.

Collection and pretreatment of human fingernail samples We obtained fingernails from 15 lung-cancer patients (age, 47–80 years; 11 men and four women) and 22 healthy volunteers (age, 41–83 years; nine men and 13 women) treated at the Fengxian Branch of the Shanghai Sixth People’s Hospital from October 2012 to January 2013. All the patients provided written informed consent before entry into the study. The fingernail samples were first rinsed with 1 mL of 0.1% SDS for 1 min by ultrasonication. The procedure was then repeated twice more. After rinsing, the SDS on the fingernail samples was removed by three washings with distilled water. The fingernails were then dried in a desiccator under reduced pressure. The dried fingernails were crushed into a powder using a Shake Master (Bio Medical Science, Tokyo, Japan).

The experimental procedures were conducted in accordance with the ethical standards of the Helsinki Declaration and were approved by the Ethics Committee of the University of Shizuoka and Fengxian Branch of the Shanghai Sixth People’s Hospital.

Validation of the method

Calibration curve preparation

Thirty microliters of two diacetylpolyamines in water (each 0.4–100 ng mL–1) were mixed with 30 µL of 2.0 ng mL–1 DAH (IS) in water. The solutions were reacted at 60°C for 30 min with 150 µL of 9.81 mg mL–1 DBD-F and 90 µL of 0.1 M borax (pH 9.3). After the reaction, 5 µL of each of the solutions was subjected to the LC-MS/MS system. The amounts corresponding to an injection of 5 µL were 0.04–10 ng mL–1 (n = 5). The calibration curves were obtained by plotting the peak area ratios of the analytes relative to the DAH (IS) versus the injected amounts of the two diacetylpolyamines. The precision [coefficient of variation (CV), %] for each concentration was also calculated from the five replicated determinations.

Accuracy and precision of intra-day and inter-day assays The accuracy (%) and precision (CV) of the intra-day and inter-day assays were determined using the standard diacetylpolyamines described in the section Calibration curve preparation. These parameters were evaluated using three different concentrations in the range 0.04–10 ng mL–1 for the diacetylpolyamines. The determinations were repeated five times within one day and between days. Each 30 µL solution was reacted with DBD-F and then subjected to the UPLC-ESI-MS/MS system, as described in the section Derivatizing the polyamines with DBD-F. The accuracy (%) at each concentration was calculated from the calibration curves described in the section Calibration curve preparation. The precision (CV, %) for each concentration was also calculated from the standard deviation values of five replicated determinations.

480

Rapid and Sensitive Determination of Diacetylpolyamines in the Human Fingernail by UPLC-ESI-MS/MS

Limit of detection The limit of detection (LOD) was defined as the calculated concentration at a signal-to-noise ratio of five (S/N = 5). The standard solutions of the diacetylpolyamines were diluted to a series of concentrations (1–100 pg mL–1). Each 30 µL solution was reacted with DBD-F and then subjected to the UPLCESI-MS/MS system, as described in the section Derivatizing the polyamines with DBD-F. The LODs of each of the diacetylpolyamines were calculated from a comparison of the noise level and the peak height on the specific mass chromatogram that had detected the target and the diacetylpolyamines.

Determining the diacetylpolyamines spiked into human fingernails and evaluation of the matrix effects Twenty microliters of the two diacetylpolyamine mixtures were added to water (2.0 ng mL–1, 4.0 ng mL–1 and 10 ng mL–1), Thirty microliters of the 2.0 ng mL–1 IS in water and 950 µL of MeOH/5 M HCl (20:1) were poured into glass vials containing 2.0 mg of the fingernails. The mixture was ultrasonically treated at room temperature three times for 15 min to extract the diacetylpolyamines, vortex-mixed for 30 s and centrifuged at 3000 × g for 2 min. After the extraction, the nail samples were washed with MeOH/5 M HCl (200 µL, twice), and all the supernatant fluids were collected and dried under a gentle stream of nitrogen gas in temperature. The resulting residues were redissolved in 150 µL of 0.1 M borax (pH 9.3) and reacted with 150 µL of 9.81 mg mL–1 DBD-F in CH3CN at 60oC for 30 min. Each 5 µL portion of the reaction mixtures was then subjected to the UPLC-ESI-MS/MS system. The recovery (%) and precision

(CV, %) of the three concentration sets (n = 5) were calculated from the calibration curve obtained by the method described in the section Calibration curve preparation.

Determination and quantification of diacetylpolyamines in the human fingernail Thirty microliters of 2.0 ng mL–1 IS in water and 970 µL of MeOH/5 M HCl (20:1) were added to 2.0 mg of each of the 15 lung-cancer patients and 25 healthy volunteer samples. The extraction and the derivatization were performed as described in the section Determining the diacetylpolyamines spiked into human fingernails and evaluation of the matrix effects. Furthermore, the amounts of diacetylpolyamines in the fingernails of the healthy volunteers and lung-cancer patients were calculated from the standard addition calibration curve obtained by the method described in the section Calibration curve preparation.

Statistical analysis The statistical analyses were performed using the Welch’s t-test or the Mann–Whitney’s U-test. A p value of  0.9999) with five different concentrations for each substance. The determination at each concentration was repeated five times. A good calibration curve was obtained for each polyamine. The detection limits (S/N = 5) in the MS were 5–10 pg mL–1. To evaluate the present method, the accuracy (%) and the precision (CV) were determined. The accuracies (%) and precisions (CVs, %) for three different concentrations were evaluated using the intra-day and interday assays. As shown in Table 1, the accuracies of the intra-day and inter-day determinations were 91.12–103.3% and 88.05– 102.9%, respectively. The CVs of the intra-day and inter-day

Among the biological specimens screened for the diacetylpolyamine assays, noninvasive urine and saliva were the most extensively investigated.5,7,28 However, the inherent problems with urine specimens, such as the fluctuation in its composition during the day and hygienic practice during its collection and handling, prompted us to search for other types of noninvasive samples. On the other hand, saliva gained much attention for clinical examination and therapeutic drug monitoring,30 because it ensures quick, noninvasive, easy, repeatable and stress-free sampling. Furthermore, saliva samples are reasonably clean and can be easily stored. In contrast, the human fingernail is relatively clean and the samples can be quickly and noninvasively collected and easily stored. Furthermore, analyzing the components of fingernails

Figure 5. Remaining diacetylpolyamines after extracting with the MeOH/5 M HCl solution at ultrasonication for 15 min. Extraction numbers­, 1 to 4.

J.Z. Min et al., Eur. J. Mass Spectrom. 20, 477–486 (2014) 483

Table 1. Accuracy and precision of the proposed method for intra-day and inter-day assays.

Diacetylpolyamines

DiAct-Spd

DiAct-Spm

Amount (ng mL-1)

Intraday assay

Interday assay

Mean ± SD

CV% (n = 5)

Accuracy (%)

Mean ± SD

CV% (n = 5)

Accuracy (%)

0.10

0.0954 ± 0.0054

5.75

 95.35

0.0908 ± 0.0056

6.19

 90.81

2.0

2.067 ± 0.134

6.50

103.30

2.058 ± 0.0519

2.56

102.90

10

9.833 ± 0.552

5.62

98.33

10.05 ± 0.2659

2.65

100.50

0.10

0.0911 ± 0.0058

6.26

 91.12

0.0881 ± 0.0032

3.66

 88.05

2.0

2.008 ± 0.142

7.06

100.40

2.042 ± 0.028

1.37

102.10

10

9.799 ± 0.536

5.47

 97.99

10.01 ± 0.208

2.07

100.10

Recovery (%)

Mean recovery (%)

CV (%)

75.69 ± 6.51

79.18

7.08

Table 2. Recovery and precision of diacetylpolyamines spiked in human fingernails using the proposed method.

Diacetylpolyamines

DiAct-Spd

DiAct-Spm

Spiked amount (pg/mg)

Detection amount (pg/mg)

  0

12.06

 20

27.20 ± 2.51

 40

43.86 ± 3.60

79.50 ± 3.40

5.36

100

94.41 ± 4.52

82.35 ± 1.55

2.20

  0

7.23

 20

23.88 ± 1.98

83.26 ± 7.80

 40

48.15 ± 4.45

102.30 ± 8.79

7.16

100

113.03 ± 5.81

105.80 ± 3.15

3.54

provides an important means of determining the individual’s past history of long-term chemical exposures, because many substances can be detected in the fingernail.8–10,12,13. However, determination at the same time of various diacetylpolyamines in the human fingernail has not yet been performed. In this study, the determination of diacetylpolyamines contained in the fingernails of lung-cancer patients and healthy volunteers was performed. The extracted diacetylpolyamines from human fingernails were reacted with DBD-F and then subjected to the

97.11

8.43

UPLC‑ESI-MS/MS system. Figure 6(a) shows the MRM mass chromatograms obtained from the diacetylpolyamines in the fingernails of the healthy volunteers. Figure 6(b) shows the MRM mass chromatograms derived from the LC-ESI-MS/MS analysis of diacetylpolyamines in the fingernails of the lungcancer patients. The peaks corresponding to the diacetylpolyamine derivatives were completely separated without any interference by the endogenous substances in the samples. The peaks corresponding to the diacetylpolyamines including the IS were eluted from 1.0 min to 3.0 min.

Figure 6. MRM mass chromatograms obtained from DBD-labeled diacetylpolyamines in fingernails from healthy volunteers (a) and lung-cancer patients (b).

484

Rapid and Sensitive Determination of Diacetylpolyamines in the Human Fingernail by UPLC-ESI-MS/MS

Table 3. Amounts of diacetylpolyamines in the fingernails from 15 lung-cancer patients and 22 healthy volunteers.

Diacetylpolyamines

H-M

H-W

HV

LCP-M

Mean ± SD (pg/mg fingernail)

LCP-W

LCP

Mean ± SD (pg/mg fingernail)

DiAct-Spd

10.11 ± 6.78

9.51 ± 3.76

9.76 ± 5.07

14.17 ± 7.12

15.35 ± 5.33

14.48 ± 6.53

DiAct-Spm

6.25 ± 4.62

10.65 ± 5.53

8.85 ± 6.01

9.70 ± 8.46

8.03 ± 5.76

9.25 ± 7.67

H-M, healthy men (50–81years, nine); H-W, healthy women (41–83 years, 13); HV, healthy volunteers; LCP-M, male lung-cancer patients (47–78 years, 11); LCP-W, female lung-cancer patients (56–80 years, four); LCP, lung cancer patients.

Concentration of diacetylpolyamines in the fingernails of lung cancer patients and healthy volunteers A total of 37 fingernail samples from lung cancer patients (age, 47–80 years; 11 men and four women) and 22 healthy volunteers (age, 41–83 years; nine men and 13 women) were analyzed. The diacetylpolyamine concentration was different based on the gender; Table 3 shows the amounts of diacetylpolyamines in fingernails from the lung-cancer patients and the healthy volunteers. The mean amounts of 10.11 pg mg–1 (DiAct-Spd) and 6.25 pg mg–1 (DiAct-Spm) in the healthy men (n = 9), 9.51 pg mg–1 (DiAct-Spd) and 10.65 pg mg–1 (DiAct-Spm) in the healthy women (n = 13), and 9.76 pg mg–1 (DiAct-Spd) and 8.85 pg mg–1 (DiAct-Spm) in the healthy volunteers (n = 22) were calculated from each calibration curve. On the other hand, the amounts for the lung-cancer patients were 14.17 pg mg–1 (DiAct-Spd) and 9.70 pg mg–1 (DiAct-Spm) in the men with lung cancer (n = 11), 15.35 pg mg–1 (DiAct-Spd) and 8.03 pg mg–1 (DiAct-Spm) in the women with lung cancer (n = 4), and 14.48 pg mg–1 (DiAct-Spd) and 9.25 pg mg–1 (DiAct-Spm) in the patients with lung cancer (n = 15). In the fingernails of the male lung-cancer patients, the diacetylpolyamine was significantly increased. Diacetylpolyamine was also found to be different between the male lung-cancer patient group and the male healthy group. However, when the healthy women were compared with the women with lung cancer, the DiAct-Spm concentrations were higher in the women with lung cancer than in the healthy women, whereas the DiAct-Spd concentrations were higher in the healthy women than in the women with lung cancer. In the lung-cancer patients, the diacetylpolyamine concentrations were not statistically different from those of the healthy volunteers. Although the biochemical mechanisms responsible for these peculiar lung-cancer patients’ diacetylpolyamine profiles are unclear, the individual sample difference seems to be another factor that affects the concentration difference.

Conclusion A sensitive and accurate UPLC-ESI-MS/MS assay for the quantification of diacetylpolyamines in human fingernails was developed and validated. Using this method, the amounts of diacetylpolyamines in the fingernails of healthy volunteers and lung-cancer patients were determined, and the derivatives of the diacetylpolyamines in the human fingernails

were successfully identified by the proposed procedure. The diacetylpolyamine amounts were also found to be different between the lung-cancer patients and the healthy volunteers. When comparing the index from the lung cancer patients with that of the healthy volunteers, the DiAct-Spd level was higher in the lung cancer patients. Therefore, this method can be applied for a sensitive detection of diacetylpolyamines in the fingernails of cancer patients. Studies of the diacetylpolyamines from the fingernails of patients with different cancers are now underway in our laboratory.

Acknowledgments The present research was supported in part by a Grantin-Aid for Challenging Exploratory Research (KAKENHI, No. 25560058; No. 26713021) from the Japan Society for the Promotion of Science, and the National Natural Science Foundation of China (No. 81360487; 21365022).

References 1. P. Coffino, “Regulation of cellular polyamines by

antizyme”, Nat. Rev. Mol. Cell Biol. 2, 188 (2001). doi: http://dx.doi.org/10.1038/35056508 2. M. Kawakita and K. Hiramatsu, “Diacetylated derivatives of spermine and spermidine as novel promising tumor markers”, J. Biochem. 139, 315 (2006). doi: http://dx.doi. org/10.1093/jb/mvj068 3. K. Yamaguchi, M. Nakamura, K. Shirahane, H. Konomi, N. Torata, N. Hamasaki, M. Kawakita and M. Tanaka, “Urine diacetylspermine as a novel tumour maker for pancreatobiliary carcinomas”, Dig. Liver. Dis. 37, 190 (2005). doi: http://dx.doi.org/10.1016/j.dld.2004.10.006 4. K. Hiramatsu, K. Takahashi, T. Yamaguchi, H. Matsumoto, H. Miyamoto, S. Tanaka, C. Tanaka, Y. Tamamori, M. Imajo, M. Kawaguchi, M. Toi, T. Mori and M. Kawakita, “N1,N12-Diacetylspermine as a sensitive­and specific novel marker for early- and late‑stage colorectal­and breast cancers”, Clin. Cancer. Res. 11, 2986 (2005). doi: http://dx.doi.org/ 10.1158/10780432 5. Y. Umemori, Y. Ohe, K. Kuribayashi, N. Tsuji, T. Nishidate, H. Kameshima, K. Hirata and N. Watanabe, “Evaluating the utility of N1,N12-diacetylspermine and N1,N8-

J.Z. Min et al., Eur. J. Mass Spectrom. 20, 477–486 (2014) 485

diacetylspermidine in urine as tumor markers for breast and colorectal cancers”, Clin. Chim. Acta 411, 1894 (2010). doi: http://dx.doi.org/ 10.1016/j.cca.2010.07.018 6. R.A. Casero and A.E. Pegg, “Polyamine catabolism and disease”, Biochem. J. 421, 323 (2009). doi: http://dx.doi. org/10.1042/BJ20090598 7. K. Samejima, K. Hiramatsu, K. Takahashi, M. Kawakita, M. Kobayashi, H. Tsumoto and K. Kohda, “Identification and determination of urinary acetylpolyamines in cancer patients by electrospray ionization and time-of-flight mass spectrometry”, Anal. Biochem. 401, 22 (2010). doi: http://dx.doi.org/10.1016/j.ab.2010.02.022 8. J.Z. Min, H. Yano, A. Matsumoto, H. Yu, Q. Shi, T. Higashi, S. Inagaki and T. Toyo’oka, “Simultaneous determination of polyamines in human nail as 4-(N,Ndimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole derivatives by nano-flow chip LC coupled with quadrupole time-of-flight tandem mass spectrometry”, Clin. Chim. Acta 412, 98 (2011). doi: http://dx.doi.org/10.1016/j. cca.2010.09.018 9. J.Z. Min, M. Yamamoto, H. Yu, T. Higashi and T. Toyo’oka, “Rapid and sensitive determination of the intermediates of advanced glycation end products in the human nail by ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry”, Anal. Biochem. 424, 187 (2012). doi: http://dx.doi.org/10.1016/j. ab.2012.02.025 10. J.Z. Min, A. Matsumoto, G. Li, Y-Z. Jiang, H. Yu, K. Todoroki, K. Inoue and T. Toyo’oka, “A quantitative analysis of the polyamine in lung cancer patient fingernails by LC-ESI-MS/MS”, Biomed. Chromatogr. 28, 492 (2014). doi: http://dx.doi.org/10.1002/bmc.3059 11. D. Jin, L. Wang and Y-I. Lee, “Determination of the polyamines in human toenails as 1-(5-fluoro2,4-dinitrophenyl)-4-methylpiperazine derivatives using high-performance liquid chromatography”, Microchem. J. 110, 568 (2013). doi: http://dx.doi.org/10.1016/j. microc.2013.07.006 12. J.Z. Min, S. Hatanaka, H. Yu, T. Higashi, S. Inagaki and T. Toyo’oka, “First detection of free d-amino acids in human nails by combination of derivatization and UPLC‑ESI-TOF-MS”, Anal. Methods 2, 1233 (2010). doi: http://dx.doi.org/10.1039/c0ay00373e 13. J.Z. Min, S. Hatanaka, H. Yu, T. Higashi, S. Inagaki and T. Toyo’oka, “Determination of dl-amino acids, derivatized with R(–)-4-(3-isothiocyanatopyrrolidin-1-yl)-7(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole in the nail of diabetic patients by UPLC-ESI-TOF-MS”, J. Chromatogr. B 879, 3220 (2011). doi: http://dx.doi. org/10.1016/j.jchromb.2011.02.016 14. C. Löser, U. Wunderlich and U.R. Fölsch, “Reversedphase liquid chromatographic separation and simultaneous fluorometric detection of polyamines and their monoacetyl derivatives in human and animal urine, serum and tissue samples: an improved, rapid and sensitive method for routine application”, J. Chromatogr.

430, 249 (1988). doi: http://dx.doi.org/10.1016/S03784347(00)83160-6 15. K. Hiramatsu, S. Kamei, M. Sugimoto, K. Kinoshita, K. Iwasaki and M. Kawakita, “An improved method of determining free and acetylated polyamines by HPLC involving an enzyme reactor and an electrochemical detector”, J. Biochem. 115, 584 (1994). 16. H. Inoue, K. Fukunaga, S. Munemura and Y. Tsuruta, “Simultaneous determination of free and N-acetylated polyamines in urine by semimicro high-performance liquid chromatography using 4-(5,6-dimethoxy2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride as a fluorescent labeling reagent”, Anal. Biochem. 339, 191 (2005). doi: http://dx.doi.org/10.1016/j.ab.2005.01.008 17. G.A. van den Berg, F.A.J. Muskiet, A.W. Kingma, W. van den Slik and M.R. Halie, “Simultaneous gas-chromatographic determination of free and acetyl-conjugated polyamines in urine”, Clin. Chem. 32, 1930 (1986). 18. G.G. Chen, G. Turecki and O.A. Mamer, “A quantitative GC-MS method for three major polyamines in postmortem brain cortex”, J. Mass. Spectrom. 44, 1203 (2009). doi: http://dx.doi.org/10.1002/jms.1597 19. M.J. Paik, S. Lee, K.H. Cho and K.R. Kim, “Urinary polyamines and N-acetylated polyamines in four patients with Alzheimer’ disease as their N-ethoxycarbonyl-Npentafluoropropionyl derivatives by gas chromatography-mass spectrometry in selected ion monitoring mode”, Anal. Chim. Acta 576, 55 (2006). doi: http://dx.doi. org/10.1016/j.aca.2006.01.070 20. M. Kobayashi, K. Samejima, K. Hiramatsu and M. Kawakita, “Mass spectrometric separation and determination of N1,N12-diacetylspermine in the urine of cancer patients”, Biol. Pharm. Bull. 25, 372 (2002). doi: http://dx.doi.org/10.1248/bpb.25.372 21. J.A. Byun, S.H. Lee, B.H. Jung, M.H. Choi, M.H. Moon and B.C. Chung, “Analysis of polyamines as carbamoyl derivatives in urine and serum by liquid chromatography-tandem mass spectrometry”, Biomed. Chromatogr. 22, 73 (2008). doi: http://dx.doi.org/10.1002/bmc.898 22. R. Liu, Y. Jia, W. Cheng, J. Ling, L. Liu, K. Bi and Q. Li, “Determination of polyamines in human urine by precolumn derivatization with benzoyl chloride and high-performance­liquid chromatography coupled with Q-time-of-flight mass spectrometry”, Talanta 83, 751 (2011). doi: http://dx.doi.org/10.1016/j.talanta.2010.10.039 23. S. Moriya, K. Iwasaki, K. Samejima, K. Takao, K. Kohda, K. Hiramatsu and M. Kawakita, “A mass spectrometric method to determine activities of enzymes involved in polyamine catabolism”, Anal. Chim. Acta 748, 45 (2012). doi: http://dx.doi.org/10.1016/j.aca.2012.08.031 24. K. Samejima, M. Otani, Y. Murakami, T. Oka, M. Kasai, H. Tsumoto and K. Kohda, “Electrospray ionization and time-of-flight mass spectrometric method for simultaneous determination of spermidine and spermine”, Biol. Pharm. Bull. 30, 1943 (2007). doi: http://dx.doi. org/10.1248/bpb.30.1943

486

Rapid and Sensitive Determination of Diacetylpolyamines in the Human Fingernail by UPLC-ESI-MS/MS

25. K. Hiramatsu, H. Miura, K. Sugimoto, S. Kamei, K.

28. H. Tsutsui, T. Mochizuki, K. Inoue T. Toyama, N.

Iwasaki and M. Kawakita, “Preparation of antibodies highly specific to N1,N8-diacetylspermidine, and development of an enzyme-linked immunosorbent assay (ELISA) system for its sensitive and specific detection”, J. Biochem. 121, 1134 (1997). doi: http://dx.doi. org/10.1093/oxfordjournals.jbchem.a021706 26. K. Fujiwara, Y. Kaminishi, T. Kitagawa, D. Tsuru, M. Yabuuchi, H. Kanetake and K. Nomata, “Preparation of monoclonal antibodies against N-(gmaleimidobutyryloxy)succinimide (GMBS)-conjugated acetylspermine, and development of an enzymelinked immunosorbent assay (ELISA) for N1,N12diacetylspermine”, J. Biochem. 124, 244 (1998). doi: http://dx.doi.org/10.1093/oxfordjournals.jbchem.a02 27. M. Bakke, K. Shimoji and N. Kajiyama, “N1,N12Diacetylspermine oxidase from Debaryomyces hansenii T-42: purification, characterization, molecular cloning and gene expression”, Biochim. Biophys. Acta 1774, 1395 (2007). doi: http://dx.doi.org/10.1016/j.bbapap.2007.08.010

Yoshimoto, Y. Endo, K. Todoroki, J.Z. Min and, T. Toyo’oka, “High-throughput LC-MS/MS based simultaneous determination of polyamines including N-acetylated forms in human saliva and the diagnostic approach to breast cancer patients”, Anal. Chem. 85, 11835 (2013). doi: http:// dx.doi.org/10.1021/ac402526c 29. K. Sugiura, J.Z. Min, T. Toyo’oka and S. Inagaki, “Rapid, sensitive and simultaneous determination of fluorescence-labeled polyamines in human hair by high-pressure liquid chromatography coupled with electrospray-ionization time-of-flight mass spectrometry”, J. Chromatogr. A 1205, 94 (2008). doi: http://dx.doi. org/10.1016/j.chroma.2008.08.026 30. M. Sugimoto, J. Saruta, C. Matsuki, M. To, H. Onuma, M. Kaneko, T. Soga, M. Tomita and K. Tsukinoki, “Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles”, Metabolomics 9, 454 (2013). doi: http://dx.doi. org/10.1007/s11306-012-0464-y

Rapid and sensitive determination of diacetylpolyamines in human fingernail by ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

A rapid and sensitive ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method has...
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